rs10491126

Positions:

• chr17-40748150-A-G
• chr17-40748150-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_181534.4(KRT25):​c.*127T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.031 in 577,670 control chromosomes in the GnomAD database, including 1,604 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.031 (423 hom., cov: 32)
  • Exomes 𝑓: 0.031 (1181 hom.)
• Consequence: KRT25 NM_181534.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.681

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRT25	NM_181534.4	c.*127T>C		3_prime_UTR_variant	8/8	ENST00000312150.5	NP_853512.1
KRT25	XM_011524414.2	c.*127T>C		3_prime_UTR_variant	9/9		XP_011522716.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRT25	ENST00000312150	c.*127T>C		3_prime_UTR_variant	8/8	1	NM_181534.4	ENSP00000310573.4

Frequencies

GnomAD3 genomes AF: 0.0309 AC: 4701 AN: 152224 Hom.: 415 Cov.: 32

Gnomad AFR AF: 0.00608

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.169

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.0149

Gnomad FIN AF: 0.0291

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00657

Gnomad OTH AF: 0.0220

GnomAD4 exome AF: 0.0310 AC: 13189 AN: 425328 Hom.: 1181 Cov.: 6 AF XY: 0.0285 AC XY: 6404 AN XY: 225028

Gnomad4 AFR exome AF: 0.00618

Gnomad4 AMR exome AF: 0.239

Gnomad4 ASJ exome AF: 0.00911

Gnomad4 EAS exome AF: 0.206

Gnomad4 SAS exome AF: 0.00914

Gnomad4 FIN exome AF: 0.0234

Gnomad4 NFE exome AF: 0.00621

Gnomad4 OTH exome AF: 0.0236

GnomAD4 genome AF: 0.0310 AC: 4723 AN: 152342 Hom.: 423 Cov.: 32 AF XY: 0.0360 AC XY: 2679 AN XY: 74494

Gnomad4 AFR AF: 0.00606

Gnomad4 AMR AF: 0.170

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.184

Gnomad4 SAS AF: 0.0149

Gnomad4 FIN AF: 0.0291

Gnomad4 NFE AF: 0.00659

Gnomad4 OTH AF: 0.0227

Alfa AF: 0.0208 Hom.: 286

Bravo AF: 0.0417

Asia WGS AF: 0.0870 AC: 301 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	10
DANN	Benign	0.75

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs10491126; hg19: chr17-38904402; COSMIC: COSV56444156;