rs11549951

Positions:

chr12-52519946-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_000424.4(KRT5):c.351C>T(p.Leu117=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.073 in 1,613,572 control chromosomes in the GnomAD database, including 4,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.078 ( 492 hom., cov: 31)

Exomes 𝑓: 0.072 ( 4314 hom. )

Consequence

KRT5
NM_000424.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.612

Variant links:

Genes affected

KRT5 (HGNC:6442): (keratin 5) The protein encoded by this gene is a member of the keratin gene family. The type II cytokeratins consist of basic or neutral proteins which are arranged in pairs of heterotypic keratin chains coexpressed during differentiation of simple and stratified epithelial tissues. This type II cytokeratin is specifically expressed in the basal layer of the epidermis with family member KRT14. Mutations in these genes have been associated with a complex of diseases termed epidermolysis bullosa simplex. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

KRT5 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 12-52519946-G-A is Benign according to our data. Variant chr12-52519946-G-A is described in ClinVar as [Benign]. Clinvar id is 256043.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.612 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.094 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT5	NM_000424.4 linkuse as main transcript	c.351C>T	p.Leu117=	synonymous_variant	1/9	ENST00000252242.9	NP_000415.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT5	ENST00000252242.9 linkuse as main transcript	c.351C>T	p.Leu117=	synonymous_variant	1/9	1	NM_000424.4	ENSP00000252242	P1

Frequencies

GnomAD3 genomes

AF:

0.0782

AC:

11865

AN:

151644

Hom.:

491

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0852

Gnomad AMI

AF:

0.156

Gnomad AMR

AF:

0.0981

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.0207

Gnomad SAS

AF:

0.0730

Gnomad FIN

AF:

0.0477

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0746

Gnomad OTH

AF:

0.100

GnomAD3 exomes

AF:

0.0741

AC:

18618

AN:

251090

Hom.:

874

AF XY:

0.0737

AC XY:

10002

AN XY:

135730

show subpopulations

Gnomad AFR exome

AF:

0.0851

Gnomad AMR exome

AF:

0.0916

Gnomad ASJ exome

AF:

0.133

Gnomad EAS exome

AF:

0.0195

Gnomad SAS exome

AF:

0.0749

Gnomad FIN exome

AF:

0.0456

Gnomad NFE exome

AF:

0.0756

Gnomad OTH exome

AF:

0.0841

GnomAD4 exome

AF:

0.0725

AC:

105935

AN:

1461810

Hom.:

4314

Cov.:

AF XY:

0.0725

AC XY:

52757

AN XY:

727196

show subpopulations

Gnomad4 AFR exome

AF:

0.0832

Gnomad4 AMR exome

AF:

0.0943

Gnomad4 ASJ exome

AF:

0.131

Gnomad4 EAS exome

AF:

0.0142

Gnomad4 SAS exome

AF:

0.0736

Gnomad4 FIN exome

AF:

0.0475

Gnomad4 NFE exome

AF:

0.0725

Gnomad4 OTH exome

AF:

0.0769

GnomAD4 genome

AF:

0.0783

AC:

11883

AN:

151762

Hom.:

492

Cov.:

AF XY:

0.0779

AC XY:

5777

AN XY:

74150

show subpopulations

Gnomad4 AFR

AF:

0.0855

Gnomad4 AMR

AF:

0.0981

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.0206

Gnomad4 SAS

AF:

0.0728

Gnomad4 FIN

AF:

0.0477

Gnomad4 NFE

AF:

0.0746

Gnomad4 OTH

AF:

0.0988

Alfa

AF:

0.0802

Hom.:

215

Bravo

AF:

0.0810

Asia WGS

AF:

0.0700

AC:

247

AN:

3478

EpiCase

AF:

0.0855

EpiControl

AF:

0.0841

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Epidermolysis bullosa simplex

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

2.7

DANN

Benign

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over