rs9982775

Positions:

• chr21-30829633-A-G

Variant summary

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

The NM_181606.3(KRTAP7-1):​c.66T>C​(p.His22His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.491 in 1,550,838 control chromosomes in the GnomAD database, including 188,527 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 0.49 (18327 hom., cov: 32)
  • Exomes 𝑓: 0.49 (170200 hom.)
• Consequence: KRTAP7-1 NM_181606.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.82

Genes affected

KRTAP7-1 (HGNC:18934): (keratin associated protein 7-1) Predicted to be located in intermediate filament. [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=-0.76).
• BP7: Synonymous conserved (PhyloP=-1.82 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.59 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KRTAP7-1	NM_181606.3	c.66T>C	p.His22His	synonymous_variant	1/1	ENST00000621162.1	NP_853637.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KRTAP7-1	ENST00000621162.1	c.66T>C	p.His22His	synonymous_variant	1/1	6	NM_181606.3	ENSP00000479656.1

Frequencies

GnomAD3 genomes AF: 0.487 AC: 73971 AN: 151872 Hom.: 18304 Cov.: 32

Gnomad AFR AF: 0.438

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.427

Gnomad EAS AF: 0.445

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.523

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.489

Gnomad OTH AF: 0.502

GnomAD3 exomes AF: 0.526 AC: 80354 AN: 152690 Hom.: 21731 AF XY: 0.520 AC XY: 42107 AN XY: 81000

Gnomad AFR exome AF: 0.434

Gnomad AMR exome AF: 0.709

Gnomad ASJ exome AF: 0.429

Gnomad EAS exome AF: 0.461

Gnomad SAS exome AF: 0.536

Gnomad FIN exome AF: 0.514

Gnomad NFE exome AF: 0.489

Gnomad OTH exome AF: 0.509

GnomAD4 exome AF: 0.491 AC: 686921 AN: 1398848 Hom.: 170200 Cov.: 40 AF XY: 0.492 AC XY: 339426 AN XY: 689942

Gnomad4 AFR exome AF: 0.433

Gnomad4 AMR exome AF: 0.691

Gnomad4 ASJ exome AF: 0.433

Gnomad4 EAS exome AF: 0.482

Gnomad4 SAS exome AF: 0.532

Gnomad4 FIN exome AF: 0.516

Gnomad4 NFE exome AF: 0.484

Gnomad4 OTH exome AF: 0.479

GnomAD4 genome AF: 0.487 AC: 74042 AN: 151990 Hom.: 18327 Cov.: 32 AF XY: 0.489 AC XY: 36356 AN XY: 74286

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.427

Gnomad4 EAS AF: 0.445

Gnomad4 SAS AF: 0.534

Gnomad4 FIN AF: 0.523

Gnomad4 NFE AF: 0.489

Gnomad4 OTH AF: 0.503

Alfa AF: 0.479 Hom.: 29079

Bravo AF: 0.491

Asia WGS AF: 0.497 AC: 1729 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.80

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: rs9982775; hg19: chr21-32201951;