Variant 12-52674849-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_006121.4(KRT1):c.*344C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.113 in 446,578 control chromosomes in the GnomAD database, including 3,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.10 ( 1120 hom., cov: 33)

Exomes 𝑓: 0.12 ( 2692 hom. )

Consequence

KRT1
NM_006121.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: 0.670

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 12-52674849-G-A is Benign according to our data. Variant chr12-52674849-G-A is described in ClinVar as [Benign]. Clinvar id is 309632.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.153 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT1	NM_006121.4 linkuse as main transcript	c.*344C>T		3_prime_UTR_variant	9/9	ENST00000252244.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT1	ENST00000252244.3 linkuse as main transcript	c.*344C>T		3_prime_UTR_variant	9/9	1	NM_006121.4	P1

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15636

AN:

152134

Hom.:

1120

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0255

Gnomad AMI

AF:

0.306

Gnomad AMR

AF:

0.0681

Gnomad ASJ

AF:

0.151

Gnomad EAS

AF:

0.000770

Gnomad SAS

AF:

0.0350

Gnomad FIN

AF:

0.165

Gnomad MID

AF:

0.104

Gnomad NFE

AF:

0.155

Gnomad OTH

AF:

0.102

GnomAD4 exome

AF:

0.119

AC:

35050

AN:

294326

Hom.:

2692

Cov.:

AF XY:

0.114

AC XY:

17742

AN XY:

155066

show subpopulations

Gnomad4 AFR exome

AF:

0.0227

Gnomad4 AMR exome

AF:

0.0605

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.000281

Gnomad4 SAS exome

AF:

0.0344

Gnomad4 FIN exome

AF:

0.166

Gnomad4 NFE exome

AF:

0.153

Gnomad4 OTH exome

AF:

0.112

GnomAD4 genome

AF:

0.103

AC:

15625

AN:

152252

Hom.:

1120

Cov.:

AF XY:

0.100

AC XY:

7471

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.0254

Gnomad4 AMR

AF:

0.0680

Gnomad4 ASJ

AF:

0.151

Gnomad4 EAS

AF:

0.000772

Gnomad4 SAS

AF:

0.0344

Gnomad4 FIN

AF:

0.165

Gnomad4 NFE

AF:

0.155

Gnomad4 OTH

AF:

0.101

Alfa

AF:

0.142

Hom.:

2425

Bravo

AF:

0.0929

Asia WGS

AF:

0.0210

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Bullous ichthyosiform erythroderma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 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. -

Diffuse nonepidermolytic palmoplantar keratoderma

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

Cadd

Benign

5.6

Dann

Benign

0.54

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