rs9471576

Positions:

• chr6-41336067-G-A

Variant summary

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

The NM_004828.4(NCR2):​c.53-20G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 1,608,032 control chromosomes in the GnomAD database, including 7,998 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 0.11 (1269 hom., cov: 32)
  • Exomes 𝑓: 0.082 (6729 hom.)
• Consequence: NCR2 NM_004828.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.994

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

Verdict is Benign. Variant got -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 = 0.294 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
NCR2	NM_004828.4	c.53-20G>A		intron_variant		ENST00000373089.10	NP_004819.2
NCR2	NM_001199509.2	c.53-20G>A		intron_variant			NP_001186438.1
NCR2	NM_001199510.2	c.53-20G>A		intron_variant			NP_001186439.1
NCR2	XM_017011500.2	c.77-20G>A		intron_variant			XP_016866989.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCR2	ENST00000373089.10	c.53-20G>A		intron_variant		1	NM_004828.4	ENSP00000362181.5
NCR2	ENST00000373086.3	c.53-20G>A		intron_variant		1		ENSP00000362178.3
NCR2	ENST00000373083.8	c.53-20G>A		intron_variant		1		ENSP00000362175.4

Frequencies

GnomAD3 genomes AF: 0.111 AC: 16913 AN: 152024 Hom.: 1266 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0450

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.120

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.0917

Gnomad FIN AF: 0.0237

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.0712

Gnomad OTH AF: 0.122

GnomAD3 exomes AF: 0.101 AC: 25008 AN: 246746 Hom.: 1930 AF XY: 0.0978 AC XY: 13023 AN XY: 133148

Gnomad AFR exome AF: 0.177

Gnomad AMR exome AF: 0.0987

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.323

Gnomad SAS exome AF: 0.0924

Gnomad FIN exome AF: 0.0230

Gnomad NFE exome AF: 0.0702

Gnomad OTH exome AF: 0.102

GnomAD4 exome AF: 0.0819 AC: 119204 AN: 1455888 Hom.: 6729 Cov.: 34 AF XY: 0.0817 AC XY: 59126 AN XY: 723566

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.0995

Gnomad4 ASJ exome AF: 0.122

Gnomad4 EAS exome AF: 0.330

Gnomad4 SAS exome AF: 0.0892

Gnomad4 FIN exome AF: 0.0252

Gnomad4 NFE exome AF: 0.0691

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.111 AC: 16930 AN: 152144 Hom.: 1269 Cov.: 32 AF XY: 0.111 AC XY: 8255 AN XY: 74378

Gnomad4 AFR AF: 0.178

Gnomad4 AMR AF: 0.107

Gnomad4 ASJ AF: 0.120

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.0913

Gnomad4 FIN AF: 0.0237

Gnomad4 NFE AF: 0.0712

Gnomad4 OTH AF: 0.130

Alfa AF: 0.0808 Hom.: 400

Bravo AF: 0.122

Asia WGS AF: 0.209 AC: 727 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.40

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: rs9471576; hg19: chr6-41303805; COSMIC: COSV66100273;