17-41097932-T-C

Variant names:

• chr17-41097932-T-C
• rs7217470
• NM_031960.3:c.153A>G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_031960.3(KRTAP4-8):​c.153A>G​(p.Arg51Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00452 in 1,559,164 control chromosomes in the GnomAD database, including 873 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 0.027 (442 hom., cov: 29)
  • Exomes 𝑓: 0.0026 (431 hom.)
• Consequence: KRTAP4-8 NM_031960.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.10

Genes affected

KRTAP4-8 (HGNC:17230): (keratin associated protein 4-8) Involved in aging and hair cycle. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP7: Synonymous conserved (PhyloP=-3.1 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KRTAP4-8	NM_031960.3	c.153A>G	p.Arg51Arg	synonymous_variant	Exon 1 of 1	ENST00000333822.5	NP_114166.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KRTAP4-8	ENST00000333822.5	c.153A>G	p.Arg51Arg	synonymous_variant	Exon 1 of 1	6	NM_031960.3	ENSP00000328444.4

Frequencies

GnomAD3 genomes AF: 0.0269 AC: 3370 AN: 125272 Hom.: 442 Cov.: 29

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00934

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000252

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00446

Gnomad NFE AF: 0.000347

Gnomad OTH AF: 0.0186

GnomAD3 exomes AF: 0.00678 AC: 1673 AN: 246928 Hom.: 162 AF XY: 0.00508 AC XY: 684 AN XY: 134522

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.00555

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000327

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000293

Gnomad OTH exome AF: 0.00364

GnomAD4 exome AF: 0.00256 AC: 3674 AN: 1433800 Hom.: 431 Cov.: 127 AF XY: 0.00224 AC XY: 1599 AN XY: 713086

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.00497

Gnomad4 ASJ exome AF: 0.0000394

Gnomad4 EAS exome AF: 0.0000257

Gnomad4 SAS exome AF: 0.000294

Gnomad4 FIN exome AF: 0.0000580

Gnomad4 NFE exome AF: 0.000224

Gnomad4 OTH exome AF: 0.00573

GnomAD4 genome AF: 0.0269 AC: 3377 AN: 125364 Hom.: 442 Cov.: 29 AF XY: 0.0261 AC XY: 1593 AN XY: 61040

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.00932

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000252

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000348

Gnomad4 OTH AF: 0.0184

Alfa AF: 0.0200 Hom.: 98

Bravo AF: 0.0507

EpiCase AF: 0.000382

EpiControl AF: 0.000416

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 27, 2025

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.5
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs7217470; hg19: chr17-39254184; COSMIC: COSV61564362; COSMIC: COSV61564362;