17-41583159-A-G

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.1275-19T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0078 in 1,611,632 control chromosomes in the GnomAD database, including 764 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.039 (381 hom., cov: 31)
  • Exomes 𝑓: 0.0045 (383 hom.)
• Consequence: KRT14 NM_000526.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

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=-0.88).
• BP6: Variant 17-41583159-A-G is Benign according to our data. Variant chr17-41583159-A-G is described in ClinVar as [Benign]. Clinvar id is 1600246.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT14	NM_000526.5	c.1275-19T>C		intron_variant		ENST00000167586.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT14	ENST00000167586.7	c.1275-19T>C		intron_variant		1	NM_000526.5	P1
KRT14	ENST00000441550.2	n.222-19T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0391 AC: 5919 AN: 151202 Hom.: 381 Cov.: 31

Gnomad AFR AF: 0.135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0162

Gnomad ASJ AF: 0.00663

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000626

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.000825

Gnomad OTH AF: 0.0221

GnomAD3 exomes AF: 0.0108 AC: 2703 AN: 251432 Hom.: 149 AF XY: 0.00797 AC XY: 1083 AN XY: 135910

Gnomad AFR exome AF: 0.141

Gnomad AMR exome AF: 0.00688

Gnomad ASJ exome AF: 0.00705

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000261

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000563

Gnomad OTH exome AF: 0.00603

GnomAD4 exome AF: 0.00453 AC: 6618 AN: 1460306 Hom.: 383 Cov.: 32 AF XY: 0.00388 AC XY: 2822 AN XY: 726512

Gnomad4 AFR exome AF: 0.145

Gnomad4 AMR exome AF: 0.00792

Gnomad4 ASJ exome AF: 0.00628

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.000429

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000447

Gnomad4 OTH exome AF: 0.0112

GnomAD4 genome AF: 0.0393 AC: 5945 AN: 151326 Hom.: 381 Cov.: 31 AF XY: 0.0383 AC XY: 2833 AN XY: 73936

Gnomad4 AFR AF: 0.135

Gnomad4 AMR AF: 0.0162

Gnomad4 ASJ AF: 0.00663

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000417

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000825

Gnomad4 OTH AF: 0.0219

Alfa AF: 0.0189 Hom.: 24

Bravo AF: 0.0458

Asia WGS AF: 0.0130 AC: 46 AN: 3478

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

Invitae

Jan 29, 2024

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	1.1
Dann	Benign	0.49

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs897428; hg19: chr17-39739411;