19-54906633-C-T

Variant names:

• chr19-54906633-C-T
• rs587625915
• NM_004829.7:c.181C>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004829.7(NCR1):​c.181C>T​(p.His61Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,884 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: NCR1 NM_004829.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.43

Genes affected

NCR1 (HGNC:6731): (natural cytotoxicity triggering receptor 1) Predicted to be involved in cellular defense response; regulation of natural killer cell mediated cytotoxicity; and signal transduction. Predicted to act upstream of or within defense response to virus and detection of virus. Predicted to be located in cell surface. Predicted to be part of SWI/SNF complex. Predicted to be active in plasma membrane. Biomarker of acquired immunodeficiency syndrome; anogenital venereal wart; hepatitis C; and lymphoproliferative syndrome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.039544106).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR1	NM_004829.7	c.181C>T	p.His61Tyr	missense_variant	Exon 3 of 7	ENST00000291890.9	NP_004820.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCR1	ENST00000291890.9	c.181C>T	p.His61Tyr	missense_variant	Exon 3 of 7	5	NM_004829.7	ENSP00000291890.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251392 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135894

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 6.84e-7 AC: 1 AN: 1461884 Hom.: 0 Cov.: 76 AF XY: 0.00 AC XY: 0 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.77
CADD	Benign	0.056
DANN	Benign	0.29
DEOGEN2	Benign	0.0086	.;T;T;T
Eigen	Benign	-2.1
Eigen_PC	Benign	-2.1
FATHMM_MKL	Benign	0.0078	N
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.040	T;T;T;T
MetaSVM	Benign	-1.0	T
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N;.;.;N
REVEL	Benign	0.022
Sift	Benign	1.0	T;.;.;T
Sift4G	Benign	0.75	T;T;T;T
Vest4		0.16
MutPred		0.51		Gain of phosphorylation at H61 (P = 0.062);.;Gain of phosphorylation at H61 (P = 0.062);Gain of phosphorylation at H61 (P = 0.062);
MVP		0.11
MPC		0.14
ClinPred		0.033	T
GERP RS		-7.8
gMVP		0.19

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs587625915; hg19: chr19-55417991;