rs2278428

Positions:

• chr19-54906696-C-A

Variant summary

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

The NM_004829.7(NCR1):​c.244C>A​(p.Gln82Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 1,614,136 control chromosomes in the GnomAD database, including 659,633 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.91 (63021 hom., cov: 32)
  • Exomes 𝑓: 0.90 (596612 hom.)
• Consequence: NCR1 NM_004829.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.756

Genes affected

NCR1 (HGNC:6731): (natural cytotoxicity triggering receptor 1) Predicted to be involved in cellular defense response; regulation of natural killer cell mediated cytotoxicity; and signal transduction. Predicted to act upstream of or within defense response to virus and detection of virus. Predicted to be located in cell surface. Predicted to be part of SWI/SNF complex. Predicted to be active in plasma membrane. Biomarker of acquired immunodeficiency syndrome; anogenital venereal wart; hepatitis C; and lymphoproliferative syndrome. [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 (MetaRNN=0.005638659).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCR1	NM_004829.7	c.244C>A	p.Gln82Lys	missense_variant	3/7	ENST00000291890.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCR1	ENST00000291890.9	c.244C>A	p.Gln82Lys	missense_variant	3/7	5	NM_004829.7	A2

Frequencies

GnomAD3 genomes AF: 0.907 AC: 137965 AN: 152134 Hom.: 62966 Cov.: 32

Gnomad AFR AF: 0.965

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.837

Gnomad ASJ AF: 0.867

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.776

Gnomad FIN AF: 0.893

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.922

Gnomad OTH AF: 0.889

GnomAD4 exome AF: 0.901 AC: 1317161 AN: 1461884 Hom.: 596612 Cov.: 90 AF XY: 0.898 AC XY: 653158 AN XY: 727244

Gnomad4 AFR exome AF: 0.967

Gnomad4 AMR exome AF: 0.770

Gnomad4 ASJ exome AF: 0.864

Gnomad4 EAS exome AF: 0.616

Gnomad4 SAS exome AF: 0.805

Gnomad4 FIN exome AF: 0.900

Gnomad4 NFE exome AF: 0.924

Gnomad4 OTH exome AF: 0.884

GnomAD4 genome AF: 0.907 AC: 138077 AN: 152252 Hom.: 63021 Cov.: 32 AF XY: 0.901 AC XY: 67068 AN XY: 74430

Gnomad4 AFR AF: 0.965

Gnomad4 AMR AF: 0.837

Gnomad4 ASJ AF: 0.867

Gnomad4 EAS AF: 0.630

Gnomad4 SAS AF: 0.777

Gnomad4 FIN AF: 0.893

Gnomad4 NFE AF: 0.922

Gnomad4 OTH AF: 0.887

Alfa AF: 0.910 Hom.: 153691

Bravo AF: 0.907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0080
DEOGEN2	Benign	0.00049	.;T;T;T
MetaRNN	Benign	0.0056	T;T;T;T
Sift4G	Benign	1.0	T;T;T;T
Vest4		0.12
gMVP		0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs2278428; hg19: chr19-55418054;