dbSNP rs2013109: RNASE2:c.-6+95G>C (chr14-20955631-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_002934.3(RNASE2):c.-6+95G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,127,990 control chromosomes in the GnomAD database, including 36,899 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 0.20 ( 3595 hom., cov: 32)

Exomes 𝑓: 0.26 ( 33304 hom. )

Consequence

RNASE2
NM_002934.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.137

Publications

11 publications found

Variant links:

Genes affected

RNASE2 (HGNC:10045): (ribonuclease A family member 2) The protein encoded by this gene is a non-secretory ribonuclease that belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein antimicrobial activity against viruses. [provided by RefSeq, Oct 2014]

RNASE2 links:

ENSG00000259130 (HGNC:):

ENSG00000259130 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.357 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002934.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASE2	NM_002934.3	MANE Select	c.-6+95G>C		intron	N/A	NP_002925.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
RNASE2	ENST00000304625.3	TSL:1 MANE Select	c.-6+95G>C	intron	N/A	ENSP00000303276.2
ENSG00000259130	ENST00000717680.1		n.346+21993C>G	intron	N/A
ENSG00000259130	ENST00000796665.1		n.772+15975C>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.201

AC:

30610

AN:

151988

Hom.:

3595

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0817

Gnomad AMI

AF:

0.319

Gnomad AMR

AF:

0.189

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.370

Gnomad SAS

AF:

0.323

Gnomad FIN

AF:

0.217

Gnomad MID

AF:

0.228

Gnomad NFE

AF:

0.248

Gnomad OTH

AF:

0.214

GnomAD4 exome

AF:

0.256

AC:

250248

AN:

975884

Hom.:

33304

Cov.:

AF XY:

0.258

AC XY:

126989

AN XY:

492384

show subpopulations

African (AFR)

AF:

0.0760

AC:

1687

AN:

22192

American (AMR)

AF:

0.206

AC:

5707

AN:

27670

Ashkenazi Jewish (ASJ)

AF:

0.274

AC:

4773

AN:

17444

East Asian (EAS)

AF:

0.374

AC:

13878

AN:

37086

South Asian (SAS)

AF:

0.314

AC:

18746

AN:

59748

European-Finnish (FIN)

AF:

0.209

AC:

9662

AN:

46138

Middle Eastern (MID)

AF:

0.249

AC:

729

AN:

2924

European-Non Finnish (NFE)

AF:

0.256

AC:

184280

AN:

719358

Other (OTH)

AF:

0.249

AC:

10786

AN:

43324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

9248

18496

27745

36993

46241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5516

11032

16548

22064

27580

<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:

0.201

AC:

30612

AN:

152106

Hom.:

3595

Cov.:

AF XY:

0.203

AC XY:

15070

AN XY:

74338

show subpopulations

African (AFR)

AF:

0.0815

AC:

3384

AN:

41516

American (AMR)

AF:

0.189

AC:

2885

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

904

AN:

3470

East Asian (EAS)

AF:

0.370

AC:

1908

AN:

5150

South Asian (SAS)

AF:

0.323

AC:

1558

AN:

4824

European-Finnish (FIN)

AF:

0.217

AC:

2289

AN:

10572

Middle Eastern (MID)

AF:

0.218

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.248

AC:

16879

AN:

67972

Other (OTH)

AF:

0.213

AC:

451

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1201

2403

3604

4806

6007

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

354

708

1062

1416

1770

<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:

0.213

Hom.:

474

Bravo

AF:

0.197

Asia WGS

AF:

0.295

AC:

1026

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

1.3

(source)

DANN

Benign

0.56

PhyloP100

0.14

PromoterAI

-0.026

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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