NM_004829.7:c.407C>T

Variant names:

• chr19-54909296-C-T
• rs769207424
• NM_004829.7:c.407C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_004829.7(NCR1):​c.407C>T​(p.Ser136Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000985 in 1,614,000 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000039 (0 hom., cov: 30)
  • Exomes 𝑓: 0.00010 (1 hom.)
• Consequence: NCR1 NM_004829.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.0480
• Publications: 0 publications found

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

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

• BP4: Computational evidence support a benign effect (MetaRNN=0.21152335).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004829.7. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCR1	NM_004829.7	MANE Select	c.407C>T	p.Ser136Leu	missense	Exon 4 of 7	NP_004820.2	O76036-1
	NCR1	NM_001145457.3		c.407C>T	p.Ser136Leu	missense	Exon 4 of 7	NP_001138929.2	A0A0A0MTU0
	NCR1	NM_001145458.3		c.407C>T	p.Ser136Leu	missense	Exon 4 of 6	NP_001138930.2	A0A0A0MR94

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	NCR1	ENST00000291890.9	TSL:5 MANE Select	c.407C>T	p.Ser136Leu	missense	Exon 4 of 7	ENSP00000291890.3	A0A0A0MQZ0
	NCR1	ENST00000338835.9	TSL:1	c.407C>T	p.Ser136Leu	missense	Exon 4 of 6	ENSP00000339515.4	O76036-2
	NCR1	ENST00000350790.9	TSL:1	c.122C>T	p.Ser41Leu	missense	Exon 3 of 6	ENSP00000344358.4	O76036-3

Frequencies

GnomAD3 genomes AF: 0.0000394 AC: 6 AN: 152118 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000119 AC: 3 AN: 251456 AF XY: 0.0000147

Gnomad AFR exome AF: 0.00

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: 0.0000264

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000105 AC: 153 AN: 1461882 Hom.: 1 Cov.: 31 AF XY: 0.000106 AC XY: 77 AN XY: 727246

African (AFR) AF: 0.0000299 AC: 1 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39698

South Asian (SAS) AF: 0.00 AC: 0 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53416

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.000133 AC: 148 AN: 1112006

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.0000394 AC: 6 AN: 152118 Hom.: 0 Cov.: 30 AF XY: 0.0000404 AC XY: 3 AN XY: 74300

African (AFR) AF: 0.00 AC: 0 AN: 41424

American (AMR) AF: 0.00 AC: 0 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4816

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68030

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.0000986 Hom.: 0

Bravo AF: 0.0000378

ExAC AF: 0.00000824 AC: 1

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.084
BayesDel_addAF	Benign	-0.36	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	3.3
DANN	Benign	0.95
DEOGEN2	Benign	0.11	T
Eigen	Benign	-0.72
Eigen_PC	Benign	-0.82
FATHMM_MKL	Benign	0.010	N
M_CAP	Benign	0.0052	T
MetaRNN	Benign	0.21	T
MetaSVM	Benign	-0.90	T
PhyloP100		0.048
PrimateAI	Benign	0.29	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Benign	0.023
Sift	Benign	0.078	T
Sift4G	Benign	0.17	T
Polyphen		0.42	B
Vest4		0.13
MVP		0.40
MPC		0.14
ClinPred		0.094	T
GERP RS		2.1
gMVP		0.19
Mutation Taster		=98/2	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: rs769207424; hg19: chr19-55420655; COSMIC: COSV105109946; COSMIC: COSV105109946;