rs2736191

Variant names:

• chr6-31593133-C-G
• rs2736191
• NM_147130.3:c.-412G>C

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP5 BP4 BA1

The NM_147130.3(NCR3):​c.-412G>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 291,288 control chromosomes in the GnomAD database, including 3,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic,risk factor (no stars).

• Frequency:
  • Genomes: 𝑓 0.13 (2297 hom., cov: 30)
  • Exomes 𝑓: 0.079 (1312 hom.)
• Consequence: NCR3 NM_147130.3 upstream_gene
• Clinical Significance: Pathogenic; risk factor no assertion criteria provided P:1 O:1
• Conservation: PhyloP100: 0.621
• Publications: 30 publications found

Genes affected

NCR3 (HGNC:19077): (natural cytotoxicity triggering receptor 3) The protein encoded by this gene is a natural cytotoxicity receptor (NCR) that may aid NK cells in the lysis of tumor cells. The encoded protein interacts with CD3-zeta (CD247), a T-cell receptor. A single nucleotide polymorphism in the 5' untranslated region of this gene has been associated with mild malaria suceptibility. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• PP5: Variant 6-31593133-C-G is Pathogenic according to our data. Variant chr6-31593133-C-G is described in ClinVar as Pathogenic|risk_factor. ClinVar VariationId is 876.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67). . Strength limited to SUPPORTING due to the PP5.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR3	NM_147130.3	c.-412G>C		upstream_gene_variant		ENST00000340027.10	NP_667341.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCR3	ENST00000340027.10	c.-412G>C		upstream_gene_variant		1	NM_147130.3	ENSP00000342156.5
NCR3	ENST00000376072.7	c.-412G>C		upstream_gene_variant		1		ENSP00000365240.3
NCR3	ENST00000376073.8	c.-412G>C		upstream_gene_variant		1		ENSP00000365241.4
NCR3	ENST00000491161.1	n.-174G>C		upstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19678 AN: 151752 Hom.: 2295 Cov.: 30

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0323

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0499

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0324

Gnomad OTH AF: 0.128

GnomAD4 exome AF: 0.0793 AC: 11054 AN: 139418 Hom.: 1312 AF XY: 0.0785 AC XY: 5732 AN XY: 73036

African (AFR) AF: 0.264 AC: 1379 AN: 5230

American (AMR) AF: 0.177 AC: 1583 AN: 8942

Ashkenazi Jewish (ASJ) AF: 0.0298 AC: 118 AN: 3956

East Asian (EAS) AF: 0.398 AC: 3495 AN: 8778

South Asian (SAS) AF: 0.0828 AC: 1494 AN: 18054

European-Finnish (FIN) AF: 0.0390 AC: 203 AN: 5202

Middle Eastern (MID) AF: 0.0696 AC: 38 AN: 546

European-Non Finnish (NFE) AF: 0.0274 AC: 2217 AN: 80914

Other (OTH) AF: 0.0676 AC: 527 AN: 7796

GnomAD4 genome AF: 0.130 AC: 19707 AN: 151870 Hom.: 2297 Cov.: 30 AF XY: 0.133 AC XY: 9846 AN XY: 74208

African (AFR) AF: 0.266 AC: 11023 AN: 41368

American (AMR) AF: 0.187 AC: 2847 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.0323 AC: 112 AN: 3470

East Asian (EAS) AF: 0.413 AC: 2117 AN: 5130

South Asian (SAS) AF: 0.120 AC: 580 AN: 4818

European-Finnish (FIN) AF: 0.0499 AC: 529 AN: 10594

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0324 AC: 2205 AN: 67956

Other (OTH) AF: 0.128 AC: 270 AN: 2108

Alfa AF: 0.0779 Hom.: 149

Bravo AF: 0.147

Asia WGS AF: 0.201 AC: 698 AN: 3478

ClinVar

Significance: Pathogenic; risk factor

Submissions summary: Pathogenic:1 Other:1

Revision: no assertion criteria provided

Submissions by phenotype

Malaria, severe, susceptibility to Pathogenic:1

Dec 06, 2022

Center for Global Health, University of New Mexico Health Sciences Center, University of New Mexico

Significance: Pathogenic

Review Status: no assertion criteria provided

Collection Method: research

CC is wild type in the Luo (Kenya) population, GG is homozygous mutant. Additive model of inheritance shows increased susceptibility to longitudinal (over 36 months) severe malarial anemia (Hb<5.0 g/dL with any density Plasmodium falciparum parasitemia) in children <48 months of age. -

Malaria, mild, susceptibility to Other:1

Feb 01, 2007

OMIM

Significance: risk factor

Review Status: no assertion criteria provided

Collection Method: literature only

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	9.5
DANN	Benign	0.72
PhyloP100		0.62
PromoterAI		0.040	Neutral

Splicing

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

Other links and lift over

dbSNP: rs2736191; hg19: chr6-31560910;