dbSNP rs2736191: NCR3:c.-89G>C (chr6-31593133-C-G) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 1P and 9B. PP5BP4BA1

The ENST00000934502.1(NCR3):c.-89G>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 0.106 in 291,288 control chromosomes in the GnomAD database, including 3,609 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Pathogenic,risk factor (no stars).

Frequency

Genomes: 𝑓 0.13 ( 2297 hom., cov: 30)

Exomes 𝑓: 0.079 ( 1312 hom. )

Consequence

NCR3
ENST00000934502.1 5_prime_UTR

Scores

Clinical Significance

Pathogenic; risk factor no assertion criteria provided P:1O:1

Conservation

PhyloP100: 0.621

Publications

31 publications found

Variant links:

Genes affected

NCR3 (HGNC:19077): (natural cytotoxicity triggering receptor 3) The protein encoded by this gene is a natural cytotoxicity receptor (NCR) that may aid NK cells in the lysis of tumor cells. The encoded protein interacts with CD3-zeta (CD247), a T-cell receptor. A single nucleotide polymorphism in the 5' untranslated region of this gene has been associated with mild malaria suceptibility. Three transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, May 2010]

NCR3 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript ENST00000934502.1, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

PP5

Variant 6-31593133-C-G is Pathogenic according to our data. Variant chr6-31593133-C-G is described in ClinVar as Pathogenic|risk_factor. ClinVar VariationId is 876.Status of the report is no_assertion_criteria_provided, 0 stars.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.67). . Strength limited to SUPPORTING due to the PP5.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.398 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000934502.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCR3	NM_147130.3	MANE Select	c.-412G>C	upstream_gene	N/A	NP_667341.1	O14931-1
NCR3	NM_001145467.2		c.-412G>C	upstream_gene	N/A	NP_001138939.1	O14931-2
NCR3	NM_001145466.2		c.-412G>C	upstream_gene	N/A	NP_001138938.1	Q05D23

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NCR3	ENST00000934502.1		c.-89G>C	5_prime_UTR	Exon 1 of 5	ENSP00000604561.1
NCR3	ENST00000934501.1		c.-194+38G>C	intron	N/A	ENSP00000604560.1
NCR3	ENST00000340027.10	TSL:1 MANE Select	c.-412G>C	upstream_gene	N/A	ENSP00000342156.5	O14931-1

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19678

AN:

151752

Hom.:

2295

Cov.:

show subpopulations

Gnomad AFR

AF:

0.267

Gnomad AMI

AF:

0.00658

Gnomad AMR

AF:

0.186

Gnomad ASJ

AF:

0.0323

Gnomad EAS

AF:

0.412

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.0499

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0324

Gnomad OTH

AF:

0.128

GnomAD4 exome

AF:

0.0793

AC:

11054

AN:

139418

Hom.:

1312

AF XY:

0.0785

AC XY:

5732

AN XY:

73036

show subpopulations

African (AFR)

AF:

0.264

AC:

1379

AN:

5230

American (AMR)

AF:

0.177

AC:

1583

AN:

8942

Ashkenazi Jewish (ASJ)

AF:

0.0298

AC:

118

AN:

3956

East Asian (EAS)

AF:

0.398

AC:

3495

AN:

8778

South Asian (SAS)

AF:

0.0828

AC:

1494

AN:

18054

European-Finnish (FIN)

AF:

0.0390

AC:

203

AN:

5202

Middle Eastern (MID)

AF:

0.0696

AC:

AN:

546

European-Non Finnish (NFE)

AF:

0.0274

AC:

2217

AN:

80914

Other (OTH)

AF:

0.0676

AC:

527

AN:

7796

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.510

Heterozygous variant carriers

395

790

1185

1580

1975

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

142

284

426

568

710

<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:

0.130

AC:

19707

AN:

151870

Hom.:

2297

Cov.:

AF XY:

0.133

AC XY:

9846

AN XY:

74208

show subpopulations

African (AFR)

AF:

0.266

AC:

11023

AN:

41368

American (AMR)

AF:

0.187

AC:

2847

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.0323

AC:

112

AN:

3470

East Asian (EAS)

AF:

0.413

AC:

2117

AN:

5130

South Asian (SAS)

AF:

0.120

AC:

580

AN:

4818

European-Finnish (FIN)

AF:

0.0499

AC:

529

AN:

10594

Middle Eastern (MID)

AF:

0.0612

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0324

AC:

2205

AN:

67956

Other (OTH)

AF:

0.128

AC:

270

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

743

1485

2228

2970

3713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

196

392

588

784

980

<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:

0.0779

Hom.:

149

Bravo

AF:

0.147

Asia WGS

AF:

0.201

AC:

698

AN:

3478

ClinVar

ClinVar submissions

Significance:Pathogenic; risk factor

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

Malaria, severe, susceptibility to (1)

Malaria, mild, susceptibility to (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

9.5

(source)

DANN

Benign

0.72

PhyloP100

0.62

PromoterAI

0.040

Neutral

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over