17-41583199-T-TG

Position:

• chr17-41583199-T-TG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_000526.5(KRT14):​c.1274+35_1274+36insC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0077 in 1,552,426 control chromosomes in the GnomAD database, including 580 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (303 hom., cov: 31)
  • Exomes 𝑓: 0.0046 (277 hom.)
• Consequence: KRT14 NM_000526.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.217

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 -10 ACMG points.

• BP6: Variant 17-41583199-T-TG is Benign according to our data. Variant chr17-41583199-T-TG is described in ClinVar as [Benign]. Clinvar id is 1221511.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.126 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT14	NM_000526.5	c.1274+35_1274+36insC		intron_variant		ENST00000167586.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT14	ENST00000167586.7	c.1274+35_1274+36insC		intron_variant		1	NM_000526.5	P1
KRT14	ENST00000441550.2	n.221+35_221+36insC		intron_variant, non_coding_transcript_variant		2
KRT14	ENST00000476662.1			downstream_gene_variant		2

Frequencies

GnomAD3 genomes AF: 0.0371 AC: 5441 AN: 146498 Hom.: 303 Cov.: 31

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00678

Gnomad EAS AF: 0.000605

Gnomad SAS AF: 0.00109

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0192

Gnomad NFE AF: 0.00107

Gnomad OTH AF: 0.0214

GnomAD3 exomes AF: 0.0102 AC: 2539 AN: 247756 Hom.: 111 AF XY: 0.00771 AC XY: 1037 AN XY: 134560

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.00696

Gnomad ASJ exome AF: 0.00735

Gnomad EAS exome AF: 0.0000547

Gnomad SAS exome AF: 0.000427

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.00113

Gnomad OTH exome AF: 0.00713

GnomAD4 exome AF: 0.00462 AC: 6488 AN: 1405816 Hom.: 277 Cov.: 32 AF XY: 0.00398 AC XY: 2791 AN XY: 701802

Gnomad4 AFR exome AF: 0.136

Gnomad4 AMR exome AF: 0.00777

Gnomad4 ASJ exome AF: 0.00641

Gnomad4 EAS exome AF: 0.000409

Gnomad4 SAS exome AF: 0.000680

Gnomad4 FIN exome AF: 0.000916

Gnomad4 NFE exome AF: 0.000705

Gnomad4 OTH exome AF: 0.0109

GnomAD4 genome AF: 0.0373 AC: 5465 AN: 146610 Hom.: 303 Cov.: 31 AF XY: 0.0367 AC XY: 2625 AN XY: 71512

Gnomad4 AFR AF: 0.129

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.00678

Gnomad4 EAS AF: 0.000606

Gnomad4 SAS AF: 0.000871

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00107

Gnomad4 OTH AF: 0.0211

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

- -

Computational scores

Source: dbNSFP v4.3

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: rs35380497; hg19: chr17-39739451;