dbSNP rs2741159: KRT1:c.963+52T>G (chr12-52677598-A-C) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_006121.4(KRT1):c.963+52T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.383 in 1,603,488 control chromosomes in the GnomAD database, including 122,818 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 11317 hom., cov: 32)

Exomes 𝑓: 0.38 ( 111501 hom. )

Consequence

KRT1
NM_006121.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2O:1

Conservation

PhyloP100: -1.67

Variant links:

Genes affected

KRT1 (HGNC:6412): (keratin 1) 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 spinous and granular layers of the epidermis with family member KRT10 and mutations in these genes have been associated with bullous congenital ichthyosiform erythroderma. The type II cytokeratins are clustered in a region of chromosome 12q12-q13. [provided by RefSeq, Jul 2008]

KRT1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 12-52677598-A-C is Benign according to our data. Variant chr12-52677598-A-C is described in ClinVar as [Benign]. Clinvar id is 66667.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.406 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRT1	NM_006121.4 link	c.963+52T>G		intron_variant	Intron 4 of 8	ENST00000252244.3	NP_006112.3	P04264

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRT1	ENST00000252244.3 link	c.963+52T>G		intron_variant	Intron 4 of 8	1	NM_006121.4	ENSP00000252244.3		P04264
KRT1	ENST00000548765.1 link	n.-81T>G		upstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57099

AN:

151982

Hom.:

11297

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.644

Gnomad AMR

AF:

0.373

Gnomad ASJ

AF:

0.383

Gnomad EAS

AF:

0.0202

Gnomad SAS

AF:

0.260

Gnomad FIN

AF:

0.408

Gnomad MID

AF:

0.316

Gnomad NFE

AF:

0.410

Gnomad OTH

AF:

0.362

GnomAD4 exome

AF:

0.384

AC:

557323

AN:

1451388

Hom.:

111501

Cov.:

AF XY:

0.380

AC XY:

274823

AN XY:

722718

show subpopulations

Gnomad4 AFR exome

AF:

0.366

Gnomad4 AMR exome

AF:

0.347

Gnomad4 ASJ exome

AF:

0.385

Gnomad4 EAS exome

AF:

0.0125

Gnomad4 SAS exome

AF:

0.256

Gnomad4 FIN exome

AF:

0.412

Gnomad4 NFE exome

AF:

0.409

Gnomad4 OTH exome

AF:

0.364

GnomAD4 genome

AF:

0.376

AC:

57151

AN:

152100

Hom.:

11317

Cov.:

AF XY:

0.369

AC XY:

27422

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.365

Gnomad4 AMR

AF:

0.373

Gnomad4 ASJ

AF:

0.383

Gnomad4 EAS

AF:

0.0202

Gnomad4 SAS

AF:

0.259

Gnomad4 FIN

AF:

0.408

Gnomad4 NFE

AF:

0.410

Gnomad4 OTH

AF:

0.370

Alfa

AF:

0.358

Hom.:

2834

Bravo

AF:

0.374

Asia WGS

AF:

0.233

AC:

809

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2Other:1

Mar 03, 2015

GeneDx

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.19

DANN

Benign

0.60

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