Genetic Variant RNASE4:c.*81T>C (chr14-20699896-T-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_002937.5(RNASE4):c.*81T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.23 in 1,224,690 control chromosomes in the GnomAD database, including 35,962 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 0.19 ( 3448 hom., cov: 32)

Exomes 𝑓: 0.24 ( 32514 hom. )

Consequence

RNASE4
NM_002937.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.182

Publications

18 publications found

Variant links:

Genes affected

RNASE4 (HGNC:10047): (ribonuclease A family member 4) The protein encoded by this gene belongs to the pancreatic ribonuclease family. It plays an important role in mRNA cleavage and has marked specificity towards the 3' side of uridine nucleotides. Alternative splicing results in four transcript variants encoding the same protein. This gene and the gene that encodes angiogenin share promoters and 5' exons. Each gene splices to a unique downstream exon that contains its complete coding region. [provided by RefSeq, Aug 2013]

RNASE4 links:

ENSG00000259171 (HGNC:):

ENSG00000259171 links:

EGILA (HGNC:54482): (EGFR interacting lncRNA)

EGILA 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 (BayesDel_noAF=-0.67).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASE4	NM_002937.5 link	c.*81T>C		3_prime_UTR_variant	Exon 2 of 2	ENST00000555835.3	NP_002928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASE4	ENST00000555835.3 link	c.*81T>C		3_prime_UTR_variant	Exon 2 of 2	1	NM_002937.5	ENSP00000452245.1
ENSG00000259171	ENST00000553909.1 link	c.*532T>C		3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000477037.1

Frequencies

GnomAD3 genomes

AF:

0.188

AC:

28594

AN:

152036

Hom.:

3453

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0495

Gnomad AMI

AF:

0.106

Gnomad AMR

AF:

0.185

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.467

Gnomad SAS

AF:

0.203

Gnomad FIN

AF:

0.242

Gnomad MID

AF:

0.174

Gnomad NFE

AF:

0.244

Gnomad OTH

AF:

0.202

GnomAD4 exome

AF:

0.236

AC:

253616

AN:

1072536

Hom.:

32514

Cov.:

AF XY:

0.237

AC XY:

128421

AN XY:

541920

show subpopulations

African (AFR)

AF:

0.0442

AC:

1146

AN:

25900

American (AMR)

AF:

0.177

AC:

7020

AN:

39710

Ashkenazi Jewish (ASJ)

AF:

0.169

AC:

3425

AN:

20280

East Asian (EAS)

AF:

0.492

AC:

18486

AN:

37548

South Asian (SAS)

AF:

0.207

AC:

14344

AN:

69250

European-Finnish (FIN)

AF:

0.238

AC:

11833

AN:

49790

Middle Eastern (MID)

AF:

0.160

AC:

707

AN:

4420

European-Non Finnish (NFE)

AF:

0.239

AC:

185918

AN:

778630

Other (OTH)

AF:

0.228

AC:

10737

AN:

47008

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

9675

19349

29024

38698

48373

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5506

11012

16518

22024

27530

<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:

0.188

AC:

28587

AN:

152154

Hom.:

3448

Cov.:

AF XY:

0.189

AC XY:

14072

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.0494

AC:

2050

AN:

41538

American (AMR)

AF:

0.185

AC:

2825

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

570

AN:

3468

East Asian (EAS)

AF:

0.466

AC:

2414

AN:

5176

South Asian (SAS)

AF:

0.203

AC:

978

AN:

4818

European-Finnish (FIN)

AF:

0.242

AC:

2560

AN:

10574

Middle Eastern (MID)

AF:

0.167

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.244

AC:

16612

AN:

67984

Other (OTH)

AF:

0.204

AC:

432

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1130

2259

3389

4518

5648

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

316

632

948

1264

1580

<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:

0.212

Hom.:

9889

Bravo

AF:

0.179

Asia WGS

AF:

0.265

AC:

921

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.67

CADD

Benign

8.1

(source)

DANN

Benign

0.83

PhyloP100

-0.18

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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