6-41335854-T-C

Variant names:

• chr6-41335854-T-C
• rs9394782
• NM_004828.4:c.-23T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004828.4(NCR2):​c.-23T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.671 in 1,559,182 control chromosomes in the GnomAD database, including 354,581 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 0.62 (30469 hom., cov: 31)
  • Exomes 𝑓: 0.68 (324112 hom.)
• Consequence: NCR2 NM_004828.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.58
• Publications: 15 publications found

Genes affected

NCR2 (HGNC:6732): (natural cytotoxicity triggering receptor 2) Predicted to enable signaling receptor activity. Predicted to be involved in cellular defense response and signal transduction. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. Predicted to be active in cell surface. [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 (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.833 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR2	NM_004828.4	c.-23T>C		5_prime_UTR_variant	Exon 1 of 5	ENST00000373089.10	NP_004819.2
NCR2	XM_017011500.2	c.2T>C	p.Met1?	start_lost	Exon 1 of 5		XP_016866989.1
NCR2	NM_001199509.2	c.-23T>C		5_prime_UTR_variant	Exon 1 of 6		NP_001186438.1
NCR2	NM_001199510.2	c.-23T>C		5_prime_UTR_variant	Exon 1 of 6		NP_001186439.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCR2	ENST00000373089.10	c.-23T>C		5_prime_UTR_variant	Exon 1 of 5	1	NM_004828.4	ENSP00000362181.5
NCR2	ENST00000373086.3	c.-23T>C		5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000362178.3
NCR2	ENST00000373083.8	c.-23T>C		5_prime_UTR_variant	Exon 1 of 6	1		ENSP00000362175.4

Frequencies

GnomAD3 genomes AF: 0.622 AC: 94457 AN: 151856 Hom.: 30461 Cov.: 31

Gnomad AFR AF: 0.443

Gnomad AMI AF: 0.704

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.613

Gnomad EAS AF: 0.855

Gnomad SAS AF: 0.666

Gnomad FIN AF: 0.712

Gnomad MID AF: 0.649

Gnomad NFE AF: 0.669

Gnomad OTH AF: 0.629

GnomAD2 exomes AF: 0.690 AC: 117453 AN: 170162 AF XY: 0.688

Gnomad AFR exome AF: 0.429

Gnomad AMR exome AF: 0.800

Gnomad ASJ exome AF: 0.644

Gnomad EAS exome AF: 0.846

Gnomad FIN exome AF: 0.708

Gnomad NFE exome AF: 0.664

Gnomad OTH exome AF: 0.695

GnomAD4 exome AF: 0.676 AC: 951426 AN: 1407208 Hom.: 324112 Cov.: 42 AF XY: 0.676 AC XY: 469887 AN XY: 694744

African (AFR) AF: 0.425 AC: 13676 AN: 32186

American (AMR) AF: 0.790 AC: 28772 AN: 36434

Ashkenazi Jewish (ASJ) AF: 0.643 AC: 16214 AN: 25224

East Asian (EAS) AF: 0.869 AC: 31904 AN: 36716

South Asian (SAS) AF: 0.681 AC: 54442 AN: 79948

European-Finnish (FIN) AF: 0.705 AC: 35057 AN: 49756

Middle Eastern (MID) AF: 0.649 AC: 3703 AN: 5708

European-Non Finnish (NFE) AF: 0.673 AC: 728669 AN: 1082832

Other (OTH) AF: 0.668 AC: 38989 AN: 58404

GnomAD4 genome AF: 0.622 AC: 94491 AN: 151974 Hom.: 30469 Cov.: 31 AF XY: 0.629 AC XY: 46697 AN XY: 74262

African (AFR) AF: 0.443 AC: 18343 AN: 41422

American (AMR) AF: 0.739 AC: 11289 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.613 AC: 2126 AN: 3470

East Asian (EAS) AF: 0.854 AC: 4387 AN: 5136

South Asian (SAS) AF: 0.664 AC: 3197 AN: 4814

European-Finnish (FIN) AF: 0.712 AC: 7534 AN: 10576

Middle Eastern (MID) AF: 0.639 AC: 188 AN: 294

European-Non Finnish (NFE) AF: 0.669 AC: 45450 AN: 67964

Other (OTH) AF: 0.633 AC: 1339 AN: 2114

Alfa AF: 0.653 Hom.: 42402

Bravo AF: 0.618

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.8
DANN	Benign	0.40
PhyloP100		-1.6
PromoterAI		-0.0035	Neutral
Mutation Taster		=300/0	polymorphism (auto)

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: rs9394782; hg19: chr6-41303592;