17-40749225-T-G

Variant summary

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

The NM_181534.4(KRT25):c.1243+33A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 1,513,698 control chromosomes in the GnomAD database, including 168,374 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.46 (16116 hom., cov: 32)
  • Exomes 𝑓: 0.47 (152258 hom.)
• Consequence: KRT25 NM_181534.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -4.18

Genes affected

KRT25 (HGNC:30839): (keratin 25) This gene encodes a member of the type I (acidic) keratin family, which belongs to the superfamily of intermediate filament (IF) proteins. Keratins are heteropolymeric structural proteins which form the intermediate filament. These filaments, along with actin microfilaments and microtubules, compose the cytoskeleton of epithelial cells. The type I keratin genes are clustered in a region of chromosome 17q12-q21. [provided by RefSeq, Jul 2009]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 17-40749225-T-G is Benign according to our data. Variant chr17-40749225-T-G is described in ClinVar as [Benign]. Clinvar id is 1225872.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT25	NM_181534.4	c.1243+33A>C		intron_variant		ENST00000312150.5
KRT25	XM_011524414.2	c.1237+33A>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT25	ENST00000312150.5	c.1243+33A>C		intron_variant		1	NM_181534.4	P1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69244 AN: 151886 Hom.: 16112 Cov.: 32

Gnomad AFR AF: 0.403

Gnomad AMI AF: 0.484

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.502

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.468

Gnomad OTH AF: 0.461

GnomAD3 exomes AF: 0.486 AC: 119597 AN: 246292 Hom.: 29918 AF XY: 0.487 AC XY: 64790 AN XY: 133142

Gnomad AFR exome AF: 0.405

Gnomad AMR exome AF: 0.414

Gnomad ASJ exome AF: 0.478

Gnomad EAS exome AF: 0.735

Gnomad SAS exome AF: 0.503

Gnomad FIN exome AF: 0.507

Gnomad NFE exome AF: 0.472

Gnomad OTH exome AF: 0.461

GnomAD4 exome AF: 0.469 AC: 638613 AN: 1361692 Hom.: 152258 Cov.: 20 AF XY: 0.470 AC XY: 320726 AN XY: 682676

Gnomad4 AFR exome AF: 0.389

Gnomad4 AMR exome AF: 0.410

Gnomad4 ASJ exome AF: 0.481

Gnomad4 EAS exome AF: 0.688

Gnomad4 SAS exome AF: 0.502

Gnomad4 FIN exome AF: 0.504

Gnomad4 NFE exome AF: 0.461

Gnomad4 OTH exome AF: 0.471

GnomAD4 genome AF: 0.456 AC: 69277 AN: 152006 Hom.: 16116 Cov.: 32 AF XY: 0.456 AC XY: 33910 AN XY: 74304

Gnomad4 AFR AF: 0.403

Gnomad4 AMR AF: 0.398

Gnomad4 ASJ AF: 0.482

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.502

Gnomad4 NFE AF: 0.468

Gnomad4 OTH AF: 0.465

Alfa AF: 0.457 Hom.: 17152

Bravo AF: 0.446

Asia WGS AF: 0.575 AC: 1999 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

GeneDx

Nov 12, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.59
Dann	Benign	0.35

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: rs10491127; hg19: chr17-38905477; COSMIC: COSV56443700;