rs4971088

Positions:

• chr1-155170407-T-A
• chr1-155170407-T-C
• chr1-155170407-T-G

Variant summary

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

The NM_173852.4(KRTCAP2):​c.224-550A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 150,220 control chromosomes in the GnomAD database, including 24,112 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 0.56 (24097 hom., cov: 28)
  • Exomes 𝑓: 0.43 (15 hom.)
• Consequence: KRTCAP2 NM_173852.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.906

Genes affected

KRTCAP2 (HGNC:28942): (keratinocyte associated protein 2) Enables enzyme activator activity. Involved in protein N-linked glycosylation via arginine. Is active in oligosaccharyltransferase complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KRTCAP2	NM_173852.4	c.224-550A>T		intron_variant		ENST00000295682.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KRTCAP2	ENST00000295682.6	c.224-550A>T		intron_variant		1	NM_173852.4	P1

Frequencies

GnomAD3 genomes AF: 0.559 AC: 83820 AN: 149994 Hom.: 24052 Cov.: 28

Gnomad AFR AF: 0.672

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.600

Gnomad ASJ AF: 0.409

Gnomad EAS AF: 0.804

Gnomad SAS AF: 0.534

Gnomad FIN AF: 0.526

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.480

Gnomad OTH AF: 0.531

GnomAD4 exome AF: 0.426 AC: 52 AN: 122 Hom.: 15 Cov.: 0 AF XY: 0.443 AC XY: 31 AN XY: 70

Gnomad4 AMR exome AF: 0.500

Gnomad4 SAS exome AF: 0.833

Gnomad4 FIN exome AF: 1.00

Gnomad4 NFE exome AF: 0.360

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.559 AC: 83911 AN: 150098 Hom.: 24097 Cov.: 28 AF XY: 0.560 AC XY: 40953 AN XY: 73070

Gnomad4 AFR AF: 0.673

Gnomad4 AMR AF: 0.600

Gnomad4 ASJ AF: 0.409

Gnomad4 EAS AF: 0.803

Gnomad4 SAS AF: 0.532

Gnomad4 FIN AF: 0.526

Gnomad4 NFE AF: 0.479

Gnomad4 OTH AF: 0.529

Alfa AF: 0.355 Hom.: 920

Bravo AF: 0.574

Asia WGS AF: 0.677 AC: 2355 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.38
DANN	Benign	0.34

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: rs4971088; hg19: chr1-155142883;