chr17-40753648-C-T

Position:

• chr17-40753648-C-T

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+212G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.112 in 126,096 control chromosomes in the GnomAD database, including 837 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.11 (837 hom., cov: 25)
• Consequence: KRT25 NM_181534.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.259

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 17-40753648-C-T is Benign according to our data. Variant chr17-40753648-C-T is described in ClinVar as [Benign]. Clinvar id is 1249389.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.143 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRT25	NM_181534.4	c.669+212G>A		intron_variant		ENST00000312150.5
KRT25	XM_011524414.2	c.663+212G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRT25	ENST00000312150.5	c.669+212G>A		intron_variant		1	NM_181534.4	P1

Frequencies

GnomAD3 genomes AF: 0.112 AC: 14107 AN: 126042 Hom.: 839 Cov.: 25

Gnomad AFR AF: 0.0295

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.00763

Gnomad SAS AF: 0.139

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.170

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.138

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

GnomAD4 genome AF: 0.112 AC: 14097 AN: 126096 Hom.: 837 Cov.: 25 AF XY: 0.114 AC XY: 6712 AN XY: 59086

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.00764

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.146

Gnomad4 OTH AF: 0.137

Alfa AF: 0.111 Hom.: 133

Bravo AF: 0.0894

Asia WGS AF: 0.0480 AC: 167 AN: 3470

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	2.2
DANN	Benign	0.75

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: rs111953138; hg19: chr17-38909900;