17-41583206-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000526.5(KRT14):c.1274+29C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0311 in 1,613,036 control chromosomes in the GnomAD database, including 1,812 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (157 hom., cov: 32)
  • Exomes 𝑓: 0.032 (1655 hom.)
• Consequence: KRT14 NM_000526.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.58

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 17-41583206-G-C is Benign according to our data. Variant chr17-41583206-G-C is described in ClinVar as [Benign]. Clinvar id is 1271599.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.159 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT14	NM_000526.5	c.1274+29C>G		intron_variant		ENST00000167586.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT14	ENST00000167586.7	c.1274+29C>G		intron_variant		1	NM_000526.5	P1
KRT14	ENST00000441550.2	n.221+29C>G		intron_variant, non_coding_transcript_variant		2
KRT14	ENST00000476662.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0254 AC: 3861 AN: 152032 Hom.: 157 Cov.: 32

Gnomad AFR AF: 0.00556

Gnomad AMI AF: 0.0121

Gnomad AMR AF: 0.0195

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.00961

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.0217

Gnomad OTH AF: 0.0311

GnomAD3 exomes AF: 0.0439 AC: 11008 AN: 250964 Hom.: 623 AF XY: 0.0478 AC XY: 6487 AN XY: 135786

Gnomad AFR exome AF: 0.00552

Gnomad AMR exome AF: 0.0135

Gnomad ASJ exome AF: 0.0595

Gnomad EAS exome AF: 0.175

Gnomad SAS exome AF: 0.120

Gnomad FIN exome AF: 0.0108

Gnomad NFE exome AF: 0.0222

Gnomad OTH exome AF: 0.0368

GnomAD4 exome AF: 0.0317 AC: 46308 AN: 1460886 Hom.: 1655 Cov.: 33 AF XY: 0.0344 AC XY: 25017 AN XY: 726760

Gnomad4 AFR exome AF: 0.00521

Gnomad4 AMR exome AF: 0.0148

Gnomad4 ASJ exome AF: 0.0589

Gnomad4 EAS exome AF: 0.153

Gnomad4 SAS exome AF: 0.118

Gnomad4 FIN exome AF: 0.0106

Gnomad4 NFE exome AF: 0.0219

Gnomad4 OTH exome AF: 0.0418

GnomAD4 genome AF: 0.0254 AC: 3864 AN: 152150 Hom.: 157 Cov.: 32 AF XY: 0.0265 AC XY: 1968 AN XY: 74384

Gnomad4 AFR AF: 0.00559

Gnomad4 AMR AF: 0.0195

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.125

Gnomad4 FIN AF: 0.00961

Gnomad4 NFE AF: 0.0217

Gnomad4 OTH AF: 0.0313

Alfa AF: 0.0156 Hom.: 7

Bravo AF: 0.0241

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2015

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
Cadd	Benign	0.50
Dann	Benign	0.48

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: rs2070671; hg19: chr17-39739458; COSMIC: COSV51420615; COSMIC: COSV51420615;