dbSNP rs2233859: RNASE3:c.-5-33C>A (chr14-20891649-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_002935.3(RNASE3):c.-5-33C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.41 in 1,580,732 control chromosomes in the GnomAD database, including 139,827 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 0.34 ( 10696 hom., cov: 30)

Exomes 𝑓: 0.42 ( 129131 hom. )

Consequence

RNASE3
NM_002935.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.847

Publications

20 publications found

Variant links:

Genes affected

RNASE3 (HGNC:10046): (ribonuclease A family member 3) The protein encoded by this gene belongs to the pancreatic ribonuclease family, a subset of the ribonuclease A superfamily. The protein exhibits antimicrobial activity against pathogenic bacteria [provided by RefSeq, Oct 2014]

RNASE3 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=-0.9).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.478 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002935.3. 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
	RNASE3	NM_002935.3	MANE Select	c.-5-33C>A		intron	N/A	NP_002926.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RNASE3	ENST00000304639.4	TSL:1 MANE Select	c.-5-33C>A	intron	N/A	ENSP00000302324.3	P12724
ENSG00000259130	ENST00000717679.1		n.259-15906G>T	intron	N/A
ENSG00000259130	ENST00000717680.1		n.347-15906G>T	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.338

AC:

50931

AN:

150502

Hom.:

10690

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0952

Gnomad AMI

AF:

0.381

Gnomad AMR

AF:

0.487

Gnomad ASJ

AF:

0.346

Gnomad EAS

AF:

0.273

Gnomad SAS

AF:

0.408

Gnomad FIN

AF:

0.499

Gnomad MID

AF:

0.369

Gnomad NFE

AF:

0.423

Gnomad OTH

AF:

0.342

GnomAD2 exomes

AF:

0.415

AC:

93551

AN:

225212

AF XY:

0.418

show subpopulations

Gnomad AFR exome

AF:

0.0899

Gnomad AMR exome

AF:

0.585

Gnomad ASJ exome

AF:

0.350

Gnomad EAS exome

AF:

0.293

Gnomad FIN exome

AF:

0.503

Gnomad NFE exome

AF:

0.424

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.418

AC:

597643

AN:

1430116

Hom.:

129131

Cov.:

AF XY:

0.418

AC XY:

295963

AN XY:

708800

show subpopulations

African (AFR)

AF:

0.0816

AC:

2606

AN:

31942

American (AMR)

AF:

0.573

AC:

23258

AN:

40572

Ashkenazi Jewish (ASJ)

AF:

0.349

AC:

8295

AN:

23776

East Asian (EAS)

AF:

0.254

AC:

10035

AN:

39530

South Asian (SAS)

AF:

0.420

AC:

33607

AN:

80058

European-Finnish (FIN)

AF:

0.498

AC:

25917

AN:

52082

Middle Eastern (MID)

AF:

0.409

AC:

2099

AN:

5128

European-Non Finnish (NFE)

AF:

0.426

AC:

468208

AN:

1098066

Other (OTH)

AF:

0.401

AC:

23618

AN:

58962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.472

Heterozygous variant carriers

16893

33786

50679

67572

84465

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14316

28632

42948

57264

71580

<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:

0.338

AC:

50949

AN:

150616

Hom.:

10696

Cov.:

AF XY:

0.346

AC XY:

25443

AN XY:

73574

show subpopulations

African (AFR)

AF:

0.0949

AC:

3824

AN:

40276

American (AMR)

AF:

0.487

AC:

7404

AN:

15202

Ashkenazi Jewish (ASJ)

AF:

0.346

AC:

1198

AN:

3466

East Asian (EAS)

AF:

0.273

AC:

1408

AN:

5152

South Asian (SAS)

AF:

0.409

AC:

1958

AN:

4792

European-Finnish (FIN)

AF:

0.499

AC:

5265

AN:

10548

Middle Eastern (MID)

AF:

0.377

AC:

110

AN:

292

European-Non Finnish (NFE)

AF:

0.423

AC:

28720

AN:

67886

Other (OTH)

AF:

0.342

AC:

715

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1518

3036

4553

6071

7589

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

504

1008

1512

2016

2520

<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:

0.361

Hom.:

17637

Bravo

AF:

0.326

Asia WGS

AF:

0.323

AC:

1123

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.42

(source)

DANN

Benign

0.52

PhyloP100

-0.85

PromoterAI

0.098

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