chr11-17351974-C-G

Variant names:

• chr11-17351974-C-G
• rs988016164
• NM_001202439.3:c.5C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001202439.3(NCR3LG1):​c.5C>G​(p.Thr2Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000815 in 1,349,020 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T2K) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000048 (0 hom., cov: 30)
  • Exomes 𝑓: 0.0000033 (0 hom.)
• Consequence: NCR3LG1 NM_001202439.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.166
• Publications: 1 publications found

Genes affected

NCR3LG1 (HGNC:42400): (natural killer cell cytotoxicity receptor 3 ligand 1) B7H6 belongs to the B7 family (see MIM 605402) and is selectively expressed on tumor cells. Interaction of B7H6 with NKp30 (NCR3; MIM 611550) results in natural killer (NK) cell activation and cytotoxicity (Brandt et al., 2009 [PubMed 19528259]).[supplied by OMIM, Jan 2011]

LOC105376576 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.04300204).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR3LG1	NM_001202439.3	c.5C>G	p.Thr2Arg	missense_variant	Exon 1 of 5	ENST00000338965.9	NP_001189368.1
NCR3LG1	XM_047426906.1	c.5C>G	p.Thr2Arg	missense_variant	Exon 1 of 6		XP_047282862.1
NCR3LG1	XM_011520074.4	c.-727C>G		upstream_gene_variant			XP_011518376.1
LOC105376576	XR_931094.3	n.-108G>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCR3LG1	ENST00000338965.9	c.5C>G	p.Thr2Arg	missense_variant	Exon 1 of 5	1	NM_001202439.3	ENSP00000341637.4
NCR3LG1	ENST00000530403.1	n.5C>G		non_coding_transcript_exon_variant	Exon 1 of 6	5		ENSP00000434394.1

Frequencies

GnomAD3 genomes AF: 0.0000482 AC: 7 AN: 145282 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000175

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000156 AC: 2 AN: 127922 AF XY: 0.0000142

Gnomad AFR exome AF: 0.000394

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000332 AC: 4 AN: 1203738 Hom.: 0 Cov.: 31 AF XY: 0.00000338 AC XY: 2 AN XY: 591818

African (AFR) AF: 0.000157 AC: 4 AN: 25470

American (AMR) AF: 0.00 AC: 0 AN: 30110

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18284

East Asian (EAS) AF: 0.00 AC: 0 AN: 18630

South Asian (SAS) AF: 0.00 AC: 0 AN: 77480

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 18844

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4762

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 964116

Other (OTH) AF: 0.00 AC: 0 AN: 46042

GnomAD4 genome AF: 0.0000482 AC: 7 AN: 145282 Hom.: 0 Cov.: 30 AF XY: 0.0000283 AC XY: 2 AN XY: 70594

African (AFR) AF: 0.000175 AC: 7 AN: 39982

American (AMR) AF: 0.00 AC: 0 AN: 14552

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3374

East Asian (EAS) AF: 0.00 AC: 0 AN: 4464

South Asian (SAS) AF: 0.00 AC: 0 AN: 4290

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9386

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66034

Other (OTH) AF: 0.00 AC: 0 AN: 2010

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000567

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.70
CADD	Benign	12
DANN	Benign	0.91
DEOGEN2	Benign	0.015	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.033	N
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-0.91	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.17
PrimateAI	Uncertain	0.49	T
PROVEAN	Benign	0.36	N
REVEL	Benign	0.056
Sift	Uncertain	0.011	D
Sift4G	Benign	0.076	T
Polyphen		0.0060	B
Vest4		0.082
MutPred		0.32		Gain of methylation at T2 (P = 0.0117);
MVP		0.072
ClinPred		0.014	T
GERP RS		0.44
PromoterAI		-0.86	Under-expression
Varity_R		0.10
gMVP		0.47
Mutation Taster		=99/1	polymorphism

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

Other links and lift over

dbSNP: rs988016164; hg19: chr11-17373521;