chr17-40753652-T-C

Position:

• chr17-40753652-T-C

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.669+208A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.391 in 130,396 control chromosomes in the GnomAD database, including 9,706 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.39 (9706 hom., cov: 21)
• Consequence: KRT25 NM_181534.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.18

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=-1.02).
• BP6: Variant 17-40753652-T-C is Benign according to our data. Variant chr17-40753652-T-C is described in ClinVar as [Benign]. Clinvar id is 1283040.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.656 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT25	NM_181534.4	c.669+208A>G		intron_variant		ENST00000312150.5
KRT25	XM_011524414.2	c.663+208A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT25	ENST00000312150.5	c.669+208A>G		intron_variant		1	NM_181534.4	P1

Frequencies

GnomAD3 genomes AF: 0.391 AC: 51022 AN: 130346 Hom.: 9718 Cov.: 21

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.364

Gnomad AMR AF: 0.415

Gnomad ASJ AF: 0.426

Gnomad EAS AF: 0.677

Gnomad SAS AF: 0.387

Gnomad FIN AF: 0.533

Gnomad MID AF: 0.438

Gnomad NFE AF: 0.423

Gnomad OTH AF: 0.394

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.391 AC: 51007 AN: 130396 Hom.: 9706 Cov.: 21 AF XY: 0.398 AC XY: 24678 AN XY: 62032

Gnomad4 AFR AF: 0.249

Gnomad4 AMR AF: 0.414

Gnomad4 ASJ AF: 0.426

Gnomad4 EAS AF: 0.676

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.533

Gnomad4 NFE AF: 0.423

Gnomad4 OTH AF: 0.391

Alfa AF: 0.357 Hom.: 1294

Bravo AF: 0.340

Asia WGS AF: 0.408 AC: 1403 AN: 3446

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	-1.0
CADD	Benign	1.1
DANN	Benign	0.66

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: rs12950911; hg19: chr17-38909904;