rs6503639

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.231C>T(p.Ser77Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.297 in 1,612,034 control chromosomes in the GnomAD database, including 76,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.25 ( 5341 hom., cov: 33)

Exomes 𝑓: 0.30 ( 70750 hom. )

Consequence

KRT14
NM_000526.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4O:1

Conservation

PhyloP100: -0.432

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=-0.63).

BP6

Variant 17-41586604-G-A is Benign according to our data. Variant chr17-41586604-G-A is described in ClinVar as Benign. ClinVar VariationId is 66334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.432 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.328 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT14	NM_000526.5 link	c.231C>T	p.Ser77Ser	synonymous_variant	Exon 1 of 8	ENST00000167586.7	NP_000517.3	P02533

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT14	ENST00000167586.7 link	c.231C>T	p.Ser77Ser	synonymous_variant	Exon 1 of 8	1	NM_000526.5	ENSP00000167586.6		P02533

Frequencies

GnomAD3 genomes

AF:

0.252

AC:

38288

AN:

151686

Hom.:

5341

Cov.:

show subpopulations

Gnomad AFR

AF:

0.168

Gnomad AMI

AF:

0.188

Gnomad AMR

AF:

0.226

Gnomad ASJ

AF:

0.289

Gnomad EAS

AF:

0.00270

Gnomad SAS

AF:

0.141

Gnomad FIN

AF:

0.270

Gnomad MID

AF:

0.326

Gnomad NFE

AF:

0.331

Gnomad OTH

AF:

0.273

GnomAD2 exomes

AF:

0.241

AC:

58761

AN:

243662

AF XY:

0.245

show subpopulations

Gnomad AFR exome

AF:

0.166

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.289

Gnomad EAS exome

AF:

0.000390

Gnomad FIN exome

AF:

0.268

Gnomad NFE exome

AF:

0.331

Gnomad OTH exome

AF:

0.275

GnomAD4 exome

AF:

0.301

AC:

439824

AN:

1460230

Hom.:

70750

Cov.:

103

AF XY:

0.298

AC XY:

216096

AN XY:

726336

show subpopulations

African (AFR)

AF:

0.160

AC:

5365

AN:

33454

American (AMR)

AF:

0.163

AC:

7244

AN:

44518

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

7459

AN:

26110

East Asian (EAS)

AF:

0.000630

AC:

AN:

39690

South Asian (SAS)

AF:

0.157

AC:

13529

AN:

86224

European-Finnish (FIN)

AF:

0.272

AC:

14419

AN:

53088

Middle Eastern (MID)

AF:

0.289

AC:

1662

AN:

5754

European-Non Finnish (NFE)

AF:

0.336

AC:

372998

AN:

1111158

Other (OTH)

AF:

0.284

AC:

17123

AN:

60234

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

21190

42380

63570

84760

105950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11752

23504

35256

47008

58760

<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:

0.252

AC:

38297

AN:

151804

Hom.:

5341

Cov.:

AF XY:

0.247

AC XY:

18311

AN XY:

74216

show subpopulations

African (AFR)

AF:

0.168

AC:

6937

AN:

41184

American (AMR)

AF:

0.226

AC:

3448

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.289

AC:

1001

AN:

3468

East Asian (EAS)

AF:

0.00270

AC:

AN:

5176

South Asian (SAS)

AF:

0.141

AC:

681

AN:

4814

European-Finnish (FIN)

AF:

0.270

AC:

2862

AN:

10582

Middle Eastern (MID)

AF:

0.323

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.331

AC:

22518

AN:

67996

Other (OTH)

AF:

0.270

AC:

570

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1473

2946

4418

5891

7364

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.305

Hom.:

2360

Bravo

AF:

0.242

Asia WGS

AF:

0.0820

AC:

285

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4Other: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

- -

Jan 30, 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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.63

CADD

Benign

7.2

(source)

DANN

Benign

0.54

PhyloP100

-0.43

PromoterAI

-0.038

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over