rs11551759

chr17-41586829-G-Achr17-41586829-G-C

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_000526.5(KRT14):c.6C>T(p.Thr2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.583 in 1,583,934 control chromosomes in the GnomAD database, including 275,896 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (25985 hom., cov: 32)
  • Exomes 𝑓: 0.58 (249911 hom.)
• Consequence: KRT14 NM_000526.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 2.59

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 17-41586829-G-A is Benign according to our data. Variant chr17-41586829-G-A is described in ClinVar as [Benign]. Clinvar id is 256364.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr17-41586829-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=2.59 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.927 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT14	NM_000526.5	c.6C>T	p.Thr2=	synonymous_variant	1/8	ENST00000167586.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT14	ENST00000167586.7	c.6C>T	p.Thr2=	synonymous_variant	1/8	1	NM_000526.5	P1

Frequencies

GnomAD3 genomes AF: 0.575 AC: 87347 AN: 151934 Hom.: 25969 Cov.: 32

Gnomad AFR AF: 0.473

Gnomad AMI AF: 0.780

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.949

Gnomad SAS AF: 0.736

Gnomad FIN AF: 0.659

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.561

GnomAD3 exomes AF: 0.641 AC: 129973 AN: 202772 Hom.: 43294 AF XY: 0.637 AC XY: 70641 AN XY: 110890

Gnomad AFR exome AF: 0.461

Gnomad AMR exome AF: 0.770

Gnomad ASJ exome AF: 0.555

Gnomad EAS exome AF: 0.943

Gnomad SAS exome AF: 0.712

Gnomad FIN exome AF: 0.661

Gnomad NFE exome AF: 0.554

Gnomad OTH exome AF: 0.589

GnomAD4 exome AF: 0.584 AC: 836734 AN: 1431882 Hom.: 249911 Cov.: 73 AF XY: 0.587 AC XY: 417258 AN XY: 710308

Gnomad4 AFR exome AF: 0.471

Gnomad4 AMR exome AF: 0.757

Gnomad4 ASJ exome AF: 0.559

Gnomad4 EAS exome AF: 0.959

Gnomad4 SAS exome AF: 0.714

Gnomad4 FIN exome AF: 0.664

Gnomad4 NFE exome AF: 0.556

Gnomad4 OTH exome AF: 0.584

GnomAD4 genome AF: 0.575 AC: 87407 AN: 152052 Hom.: 25985 Cov.: 32 AF XY: 0.584 AC XY: 43393 AN XY: 74328

Gnomad4 AFR AF: 0.472

Gnomad4 AMR AF: 0.679

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.949

Gnomad4 SAS AF: 0.735

Gnomad4 FIN AF: 0.659

Gnomad4 NFE AF: 0.560

Gnomad4 OTH AF: 0.565

Alfa AF: 0.568 Hom.: 42373

Bravo AF: 0.573

Asia WGS AF: 0.822 AC: 2860 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
Cadd	Benign	12
Dann	Benign	0.94

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

Other links and lift over

dbSNP: rs11551759; hg19: chr17-39743081; COSMIC: COSV51422329; COSMIC: COSV51422329;