chr6-41335854-T-C

Position:

• chr6-41335854-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.833 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
NCR2	ENST00000373089	c.-23T>C		5_prime_UTR_variant	1/5	1	NM_004828.4	ENSP00000362181.5
NCR2	ENST00000373086	c.-23T>C		5_prime_UTR_variant	1/6	1		ENSP00000362178.3
NCR2	ENST00000373083	c.-23T>C		5_prime_UTR_variant	1/6	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

GnomAD3 exomes AF: 0.690 AC: 117453 AN: 170162 Hom.: 41279 AF XY: 0.688 AC XY: 61758 AN XY: 89700

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 SAS exome AF: 0.680

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

Gnomad4 AFR exome AF: 0.425

Gnomad4 AMR exome AF: 0.790

Gnomad4 ASJ exome AF: 0.643

Gnomad4 EAS exome AF: 0.869

Gnomad4 SAS exome AF: 0.681

Gnomad4 FIN exome AF: 0.705

Gnomad4 NFE exome AF: 0.673

Gnomad4 OTH exome AF: 0.668

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

Gnomad4 AFR AF: 0.443

Gnomad4 AMR AF: 0.739

Gnomad4 ASJ AF: 0.613

Gnomad4 EAS AF: 0.854

Gnomad4 SAS AF: 0.664

Gnomad4 FIN AF: 0.712

Gnomad4 NFE AF: 0.669

Gnomad4 OTH AF: 0.633

Alfa AF: 0.659 Hom.: 32996

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

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: rs9394782; hg19: chr6-41303592;