rs986475

Positions:

• chr6-31588932-A-G
• chr6-31588932-A-T

Variant summary

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

The NM_147130.3(NCR3):​c.*135T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0921 in 1,028,844 control chromosomes in the GnomAD database, including 5,844 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 0.088 (867 hom., cov: 32)
  • Exomes 𝑓: 0.093 (4977 hom.)
• Consequence: NCR3 NM_147130.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0690

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]

LST1 (HGNC:14189): (leukocyte specific transcript 1) The protein encoded by this gene is a membrane protein that can inhibit the proliferation of lymphocytes. Expression of this gene is enhanced by lipopolysaccharide, interferon-gamma, and bacteria. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NCR3	NM_147130.3	c.*135T>C		3_prime_UTR_variant	4/4	ENST00000340027.10
LST1	NM_205839.3			downstream_gene_variant		ENST00000438075.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NCR3	ENST00000340027.10	c.*135T>C		3_prime_UTR_variant	4/4	1	NM_147130.3	P2
LST1	ENST00000438075.7			downstream_gene_variant		1	NM_205839.3	P1

Frequencies

GnomAD3 genomes AF: 0.0882 AC: 13423 AN: 152146 Hom.: 864 Cov.: 32

Gnomad AFR AF: 0.0300

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.179

Gnomad ASJ AF: 0.247

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.0555

Gnomad MID AF: 0.146

Gnomad NFE AF: 0.0916

Gnomad OTH AF: 0.0966

GnomAD4 exome AF: 0.0928 AC: 81309 AN: 876580 Hom.: 4977 Cov.: 12 AF XY: 0.0958 AC XY: 41842 AN XY: 436990

Gnomad4 AFR exome AF: 0.0329

Gnomad4 AMR exome AF: 0.208

Gnomad4 ASJ exome AF: 0.229

Gnomad4 EAS exome AF: 0.198

Gnomad4 SAS exome AF: 0.138

Gnomad4 FIN exome AF: 0.0553

Gnomad4 NFE exome AF: 0.0807

Gnomad4 OTH exome AF: 0.100

GnomAD4 genome AF: 0.0883 AC: 13445 AN: 152264 Hom.: 867 Cov.: 32 AF XY: 0.0905 AC XY: 6738 AN XY: 74446

Gnomad4 AFR AF: 0.0299

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.247

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.134

Gnomad4 FIN AF: 0.0555

Gnomad4 NFE AF: 0.0916

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0948 Hom.: 726

Bravo AF: 0.0940

Asia WGS AF: 0.132 AC: 460 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.3
DANN	Benign	0.59

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: rs986475; hg19: chr6-31556709;