rs2278428

Variant names:

• chr19-54906696-C-A
• rs2278428
• NM_004829.7:c.244C>A
• NCR1 p.Gln82Lys

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 32 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004829.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCR1	NM_004829.7	MANE Select	c.244C>A	p.Gln82Lys	missense	Exon 3 of 7	NP_004820.2	O76036-1
	NCR1	NM_001145457.3		c.244C>A	p.Gln82Lys	missense	Exon 3 of 7	NP_001138929.2	A0A0A0MTU0
	NCR1	NM_001145458.3		c.244C>A	p.Gln82Lys	missense	Exon 3 of 6	NP_001138930.2	A0A0A0MR94

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCR1	ENST00000291890.9	TSL:5 MANE Select	c.244C>A	p.Gln82Lys	missense	Exon 3 of 7	ENSP00000291890.3	A0A0A0MQZ0
	NCR1	ENST00000338835.9	TSL:1	c.244C>A	p.Gln82Lys	missense	Exon 3 of 6	ENSP00000339515.4	O76036-2
	NCR1	ENST00000350790.9	TSL:1	c.70+362C>A		intron	N/A	ENSP00000344358.4	O76036-3

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

African (AFR) AF: 0.967 AC: 32390 AN: 33480

American (AMR) AF: 0.770 AC: 34448 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.864 AC: 22588 AN: 26136

East Asian (EAS) AF: 0.616 AC: 24442 AN: 39700

South Asian (SAS) AF: 0.805 AC: 69471 AN: 86258

European-Finnish (FIN) AF: 0.900 AC: 48054 AN: 53410

Middle Eastern (MID) AF: 0.803 AC: 4634 AN: 5768

European-Non Finnish (NFE) AF: 0.924 AC: 1027753 AN: 1112012

Other (OTH) AF: 0.884 AC: 53381 AN: 60396

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

African (AFR) AF: 0.965 AC: 40114 AN: 41556

American (AMR) AF: 0.837 AC: 12799 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.867 AC: 3009 AN: 3472

East Asian (EAS) AF: 0.630 AC: 3249 AN: 5160

South Asian (SAS) AF: 0.777 AC: 3744 AN: 4818

European-Finnish (FIN) AF: 0.893 AC: 9465 AN: 10604

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.922 AC: 62714 AN: 68022

Other (OTH) AF: 0.887 AC: 1876 AN: 2114

Alfa AF: 0.910 Hom.: 216502

Bravo AF: 0.907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.060
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.0080
DEOGEN2	Benign	0.00049	T
MetaRNN	Benign	0.0056	T
PhyloP100		-0.76
Sift4G	Benign	1.0	T
gMVP		0.18

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2278428;

hg19: chr19-55418054;