chr17-41586642-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000526.5(KRT14):c.193C>T(p.Leu65Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.585 in 1,606,622 control chromosomes in the GnomAD database, including 281,528 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.58 ( 26004 hom., cov: 33)

Exomes 𝑓: 0.59 ( 255524 hom. )

Consequence

KRT14
NM_000526.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5O:1

Conservation

PhyloP100: -1.81

Publications

10 publications found

Variant links:

Genes affected

KRT14 (HGNC:6416): (keratin 14) This gene encodes a member of the keratin family, the most diverse group of intermediate filaments. This gene product, a type I keratin, is usually found as a heterotetramer with two keratin 5 molecules, a type II keratin. Together they form the cytoskeleton of epithelial cells. Mutations in the genes for these keratins are associated with epidermolysis bullosa simplex. At least one pseudogene has been identified at 17p12-p11. [provided by RefSeq, Jul 2008]

KRT14 Gene-Disease associations (from GenCC):

epidermolysis bullosa simplex 1A, generalized severe
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Genomics England PanelApp
Naegeli-Franceschetti-Jadassohn syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Genomics England PanelApp, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
epidermolysis bullosa simplex
Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics, Genomics England PanelApp
dermatopathia pigmentosa reticularis
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 1B, generalized intermediate
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 1C, localized
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Genomics England PanelApp
epidermolysis bullosa simplex 2F, with mottled pigmentation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

KRT14 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 17-41586642-G-A is Benign according to our data. Variant chr17-41586642-G-A is described in ClinVar as Benign. ClinVar VariationId is 66332.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.81 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000526.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT14	NM_000526.5	MANE Select	c.193C>T	p.Leu65Leu	synonymous	Exon 1 of 8	NP_000517.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT14	ENST00000167586.7	TSL:1 MANE Select	c.193C>T	p.Leu65Leu	synonymous	Exon 1 of 8	ENSP00000167586.6

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87366

AN:

151922

Hom.:

25988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.561

Gnomad EAS

AF:

0.949

Gnomad SAS

AF:

0.736

Gnomad FIN

AF:

0.659

Gnomad MID

AF:

0.440

Gnomad NFE

AF:

0.560

Gnomad OTH

AF:

0.561

GnomAD2 exomes

AF:

0.632

AC:

136896

AN:

216556

AF XY:

0.630

show subpopulations

Gnomad AFR exome

AF:

0.454

Gnomad AMR exome

AF:

0.764

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.942

Gnomad FIN exome

AF:

0.657

Gnomad NFE exome

AF:

0.546

Gnomad OTH exome

AF:

0.586

GnomAD4 exome

AF:

0.586

AC:

852346

AN:

1454582

Hom.:

255524

Cov.:

AF XY:

0.589

AC XY:

426034

AN XY:

723172

show subpopulations

African (AFR)

AF:

0.472

AC:

15703

AN:

33266

American (AMR)

AF:

0.762

AC:

32986

AN:

43268

Ashkenazi Jewish (ASJ)

AF:

0.563

AC:

14634

AN:

26012

East Asian (EAS)

AF:

0.959

AC:

37812

AN:

39414

South Asian (SAS)

AF:

0.715

AC:

61434

AN:

85880

European-Finnish (FIN)

AF:

0.664

AC:

34992

AN:

52686

Middle Eastern (MID)

AF:

0.504

AC:

2811

AN:

5580

European-Non Finnish (NFE)

AF:

0.557

AC:

616880

AN:

1108444

Other (OTH)

AF:

0.585

AC:

35094

AN:

60032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

23896

47792

71688

95584

119480

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17428

34856

52284

69712

87140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.575

AC:

87426

AN:

152040

Hom.:

26004

Cov.:

AF XY:

0.584

AC XY:

43409

AN XY:

74316

show subpopulations

African (AFR)

AF:

0.472

AC:

19588

AN:

41466

American (AMR)

AF:

0.679

AC:

10368

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.561

AC:

1948

AN:

3472

East Asian (EAS)

AF:

0.949

AC:

4902

AN:

5166

South Asian (SAS)

AF:

0.736

AC:

3547

AN:

4822

European-Finnish (FIN)

AF:

0.659

AC:

6969

AN:

10570

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.560

AC:

38067

AN:

67944

Other (OTH)

AF:

0.565

AC:

1195

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

1806

3612

5419

7225

9031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

754

1508

2262

3016

3770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.562

Hom.:

7678

Bravo

AF:

0.574

Asia WGS

AF:

0.823

AC:

2857

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:5Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3Other:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Epithelial Biology; Institute of Medical Biology, Singapore

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Epidermolysis bullosa simplex 1A, generalized severe;C0080333:Epidermolysis bullosa simplex 1C, localized;C0343111:Naegeli-Franceschetti-Jadassohn syndrome;C0406778:Dermatopathia pigmentosa reticularis;C3715082:Epidermolysis bullosa simplex 1D, generalized, intermediate or severe, autosomal recessive;C5561924:Epidermolysis bullosa simplex, Koebner type

Benign:1

Aug 11, 2021

Fulgent Genetics, Fulgent Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

1.9

(source)

DANN

Benign

0.62

PhyloP100

-1.8

PromoterAI

-0.0068

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over