rs2741159

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -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

Publications

17 publications found

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 Gene-Disease associations (from GenCC):

annular epidermolytic ichthyosis
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Genomics England PanelApp, PanelApp Australia
ichthyosis hystrix of Curth-Macklin
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Genomics England PanelApp, PanelApp Australia
diffuse nonepidermolytic palmoplantar keratoderma
Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Genomics England PanelApp, Orphanet
epidermolytic ichthyosis
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Illumina, Orphanet, Genomics England PanelApp, PanelApp Australia
ichthyosis, annular epidermolytic 1
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
ichthyosis, annular epidermolytic, 2
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics
congenital reticular ichthyosiform erythroderma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
striate palmoplantar keratoderma
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
autosomal recessive congenital ichthyosis 11
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

KRT1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

African (AFR)

AF:

0.366

AC:

12154

AN:

33248

American (AMR)

AF:

0.347

AC:

15508

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.385

AC:

10034

AN:

26080

East Asian (EAS)

AF:

0.0125

AC:

494

AN:

39656

South Asian (SAS)

AF:

0.256

AC:

22006

AN:

86008

European-Finnish (FIN)

AF:

0.412

AC:

22000

AN:

53412

Middle Eastern (MID)

AF:

0.332

AC:

1912

AN:

5756

European-Non Finnish (NFE)

AF:

0.409

AC:

451352

AN:

1102516

Other (OTH)

AF:

0.364

AC:

21863

AN:

59998

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

19146

38292

57438

76584

95730

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

13608

27216

40824

54432

68040

<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:

0.376

AC:

57151

AN:

152100

Hom.:

11317

Cov.:

AF XY:

0.369

AC XY:

27422

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.365

AC:

15140

AN:

41478

American (AMR)

AF:

0.373

AC:

5701

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.383

AC:

1329

AN:

3470

East Asian (EAS)

AF:

0.0202

AC:

105

AN:

5186

South Asian (SAS)

AF:

0.259

AC:

1247

AN:

4816

European-Finnish (FIN)

AF:

0.408

AC:

4308

AN:

10562

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.410

AC:

27855

AN:

67980

Other (OTH)

AF:

0.370

AC:

782

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1803

3605

5408

7210

9013

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

540

1080

1620

2160

2700

<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:

0.360

Hom.:

4692

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

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Epithelial Biology; Institute of Medical Biology, Singapore

Significance:not provided

Review Status:no classification provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.19

(source)

DANN

Benign

0.60

PhyloP100

-1.7

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