rs11551759

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.6C>T(p.Thr2Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,583,934 control chromosomes in the GnomAD database, including 275,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.57 ( 25985 hom., cov: 32)

Exomes 𝑓: 0.58 ( 249911 hom. )

Consequence

KRT14
NM_000526.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 2.59

Publications

15 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: Genomics England PanelApp, Ambry Genetics, Orphanet
Naegeli-Franceschetti-Jadassohn syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Orphanet, Genomics England PanelApp
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), Ambry Genetics, Genomics England PanelApp, Orphanet
dermatopathia pigmentosa reticularis
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
epidermolysis bullosa simplex 1B, generalized intermediate
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet, Labcorp Genetics (formerly Invitae)
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=-0.56).

BP6

Variant 17-41586829-G-A is Benign according to our data. Variant chr17-41586829-G-A is described in ClinVar as Benign. ClinVar VariationId is 256364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.59 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT14	NM_000526.5	MANE Select	c.6C>T	p.Thr2Thr	synonymous	Exon 1 of 8	NP_000517.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KRT14	ENST00000167586.7	TSL:1 MANE Select	c.6C>T	p.Thr2Thr	synonymous	Exon 1 of 8	ENSP00000167586.6	P02533

Frequencies

GnomAD3 genomes

AF:

0.575

AC:

87347

AN:

151934

Hom.:

25969

Cov.:

show subpopulations

Gnomad AFR

AF:

0.473

Gnomad AMI

AF:

0.780

Gnomad AMR

AF:

0.678

Gnomad ASJ

AF:

0.558

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:

0.641

AC:

129973

AN:

202772

AF XY:

0.637

show subpopulations

Gnomad AFR exome

AF:

0.461

Gnomad AMR exome

AF:

0.770

Gnomad ASJ exome

AF:

0.555

Gnomad EAS exome

AF:

0.943

Gnomad FIN exome

AF:

0.661

Gnomad NFE exome

AF:

0.554

Gnomad OTH exome

AF:

0.589

GnomAD4 exome

AF:

0.584

AC:

836734

AN:

1431882

Hom.:

249911

Cov.:

AF XY:

0.587

AC XY:

417258

AN XY:

710308

show subpopulations

African (AFR)

AF:

0.471

AC:

15469

AN:

32866

American (AMR)

AF:

0.757

AC:

31021

AN:

40964

Ashkenazi Jewish (ASJ)

AF:

0.559

AC:

14375

AN:

25720

East Asian (EAS)

AF:

0.959

AC:

36619

AN:

38182

South Asian (SAS)

AF:

0.714

AC:

59322

AN:

83134

European-Finnish (FIN)

AF:

0.664

AC:

32043

AN:

48252

Middle Eastern (MID)

AF:

0.517

AC:

2129

AN:

4120

European-Non Finnish (NFE)

AF:

0.556

AC:

611172

AN:

1099464

Other (OTH)

AF:

0.584

AC:

34584

AN:

59180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.456

Heterozygous variant carriers

20130

40260

60391

80521

100651

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17308

34616

51924

69232

86540

<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:

87407

AN:

152052

Hom.:

25985

Cov.:

AF XY:

0.584

AC XY:

43393

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.472

AC:

19589

AN:

41464

American (AMR)

AF:

0.679

AC:

10380

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.558

AC:

1936

AN:

3470

East Asian (EAS)

AF:

0.949

AC:

4895

AN:

5158

South Asian (SAS)

AF:

0.735

AC:

3544

AN:

4822

European-Finnish (FIN)

AF:

0.659

AC:

6966

AN:

10574

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.560

AC:

38062

AN:

67948

Other (OTH)

AF:

0.565

AC:

1194

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1832

3664

5496

7328

9160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

756

1512

2268

3024

3780

<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:

0.566

Hom.:

66642

Bravo

AF:

0.573

Asia WGS

AF:

0.822

AC:

2860

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

2.6

PromoterAI

0.15

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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

Computational scores

Splicing

Publications

Other links and lift over