Variant rs2001185 details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_000526.5(KRT14):c.1322-13A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.119 in 1,552,686 control chromosomes in the GnomAD database, including 13,282 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2892 hom., cov: 32)

Exomes 𝑓: 0.11 ( 10390 hom. )

Consequence

KRT14
NM_000526.5 splice_polypyrimidine_tract, intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.167

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 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=-0.92).

BP6

Variant 17-41582545-T-C is Benign according to our data. Variant chr17-41582545-T-C is described in ClinVar as [Benign]. Clinvar id is 66328.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT14	NM_000526.5 linkuse as main transcript	c.1322-13A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000167586.7	NP_000517.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT14	ENST00000167586.7 linkuse as main transcript	c.1322-13A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000526.5	ENSP00000167586	P1
KRT14	ENST00000441550.2 linkuse as main transcript	n.817A>G		non_coding_transcript_exon_variant	2/2	2

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25275

AN:

151710

Hom.:

2885

Cov.:

show subpopulations

Gnomad AFR

AF:

0.332

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.0978

Gnomad ASJ

AF:

0.148

Gnomad EAS

AF:

0.0495

Gnomad SAS

AF:

0.133

Gnomad FIN

AF:

0.0747

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.110

Gnomad OTH

AF:

0.162

GnomAD3 exomes

AF:

0.119

AC:

19037

AN:

160610

Hom.:

1479

AF XY:

0.119

AC XY:

10069

AN XY:

84804

show subpopulations

Gnomad AFR exome

AF:

0.338

Gnomad AMR exome

AF:

0.0724

Gnomad ASJ exome

AF:

0.153

Gnomad EAS exome

AF:

0.0604

Gnomad SAS exome

AF:

0.144

Gnomad FIN exome

AF:

0.0705

Gnomad NFE exome

AF:

0.112

Gnomad OTH exome

AF:

0.139

GnomAD4 exome

AF:

0.114

AC:

159487

AN:

1400856

Hom.:

10390

Cov.:

AF XY:

0.115

AC XY:

79189

AN XY:

691602

show subpopulations

Gnomad4 AFR exome

AF:

0.344

Gnomad4 AMR exome

AF:

0.0760

Gnomad4 ASJ exome

AF:

0.152

Gnomad4 EAS exome

AF:

0.0413

Gnomad4 SAS exome

AF:

0.143

Gnomad4 FIN exome

AF:

0.0662

Gnomad4 NFE exome

AF:

0.109

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.167

AC:

25320

AN:

151830

Hom.:

2892

Cov.:

AF XY:

0.164

AC XY:

12134

AN XY:

74174

show subpopulations

Gnomad4 AFR

AF:

0.332

Gnomad4 AMR

AF:

0.0975

Gnomad4 ASJ

AF:

0.148

Gnomad4 EAS

AF:

0.0493

Gnomad4 SAS

AF:

0.134

Gnomad4 FIN

AF:

0.0747

Gnomad4 NFE

AF:

0.110

Gnomad4 OTH

AF:

0.164

Alfa

AF:

0.140

Hom.:

343

Bravo

AF:

0.177

Asia WGS

AF:

0.108

AC:

375

AN:

3476

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -
not provided, no classification provided	literature only	Epithelial Biology; Institute of Medical Biology, Singapore	-	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.9

DANN

Benign

0.37

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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