Genetic Variant NM_004829.7:c.244C>A (chr19-54906696-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004829.7(NCR1):c.244C>A(p.Gln82Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.902 in 1,614,136 control chromosomes in the GnomAD database, including 659,633 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/6 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: 𝑓 0.91 ( 63021 hom., cov: 32)

Exomes 𝑓: 0.90 ( 596612 hom. )

Consequence

NCR1
NM_004829.7 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.756

Publications

31 publications found

Variant links:

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]

NCR1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005638659).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.957 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NCR1	NM_004829.7 link	c.244C>A	p.Gln82Lys	missense_variant	Exon 3 of 7	ENST00000291890.9	NP_004820.2	O76036A0A0A0MQZ0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NCR1	ENST00000291890.9 link	c.244C>A	p.Gln82Lys	missense_variant	Exon 3 of 7	5	NM_004829.7	ENSP00000291890.3		A0A0A0MQZ0

Frequencies

GnomAD3 genomes

AF:

0.907

AC:

137965

AN:

152134

Hom.:

62966

Cov.:

show subpopulations

Gnomad AFR

AF:

0.965

Gnomad AMI

AF:

0.956

Gnomad AMR

AF:

0.837

Gnomad ASJ

AF:

0.867

Gnomad EAS

AF:

0.630

Gnomad SAS

AF:

0.776

Gnomad FIN

AF:

0.893

Gnomad MID

AF:

0.807

Gnomad NFE

AF:

0.922

Gnomad OTH

AF:

0.889

GnomAD4 exome

AF:

0.901

AC:

1317161

AN:

1461884

Hom.:

596612

Cov.:

AF XY:

0.898

AC XY:

653158

AN XY:

727244

show subpopulations

African (AFR)

AF:

0.967

AC:

32390

AN:

33480

American (AMR)

AF:

0.770

AC:

34448

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.864

AC:

22588

AN:

26136

East Asian (EAS)

AF:

0.616

AC:

24442

AN:

39700

South Asian (SAS)

AF:

0.805

AC:

69471

AN:

86258

European-Finnish (FIN)

AF:

0.900

AC:

48054

AN:

53410

Middle Eastern (MID)

AF:

0.803

AC:

4634

AN:

5768

European-Non Finnish (NFE)

AF:

0.924

AC:

1027753

AN:

1112012

Other (OTH)

AF:

0.884

AC:

53381

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.520

Heterozygous variant carriers

9542

19084

28627

38169

47711

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21468

42936

64404

85872

107340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.907

AC:

138077

AN:

152252

Hom.:

63021

Cov.:

AF XY:

0.901

AC XY:

67068

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.965

AC:

40114

AN:

41556

American (AMR)

AF:

0.837

AC:

12799

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.867

AC:

3009

AN:

3472

East Asian (EAS)

AF:

0.630

AC:

3249

AN:

5160

South Asian (SAS)

AF:

0.777

AC:

3744

AN:

4818

European-Finnish (FIN)

AF:

0.893

AC:

9465

AN:

10604

Middle Eastern (MID)

AF:

0.799

AC:

235

AN:

294

European-Non Finnish (NFE)

AF:

0.922

AC:

62714

AN:

68022

Other (OTH)

AF:

0.887

AC:

1876

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

632

1263

1895

2526

3158

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.910

Hom.:

216502

Bravo

AF:

0.907

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.060

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.0080

(source)

DEOGEN2

Benign

0.00049

.;T;T;T

MetaRNN

Benign

0.0056

T;T;T;T

PhyloP100

-0.76

Sift4G

Benign

1.0

T;T;T;T

Vest4

0.12

gMVP

0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over