dbSNP rs3777722: RNASET2:c.446+279G>T (chr6-166938616-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_003730.6(RNASET2):c.446+279G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.141 in 687,686 control chromosomes in the GnomAD database, including 10,582 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 0.11 ( 1552 hom., cov: 33)

Exomes 𝑓: 0.15 ( 9030 hom. )

Consequence

RNASET2
NM_003730.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0370

Publications

22 publications found

Variant links:

Genes affected

RNASET2 (HGNC:21686): (ribonuclease T2) This ribonuclease gene is a novel member of the Rh/T2/S-glycoprotein class of extracellular ribonucleases. It is a single copy gene that maps to 6q27, a region associated with human malignancies and chromosomal rearrangement. [provided by RefSeq, Jul 2008]

RNASET2 Gene-Disease associations (from GenCC):

cystic leukoencephalopathy without megalencephaly
Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae), Illumina, PanelApp Australia, Orphanet

RNASET2 links:

ENSG00000249141 (HGNC:):

ENSG00000249141 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 (MetaRNN=0.003393352).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.387 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RNASET2	NM_003730.6 link	c.446+279G>T		intron_variant	Intron 6 of 8	ENST00000508775.6	NP_003721.2	O00584-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RNASET2	ENST00000508775.6 link	c.446+279G>T		intron_variant	Intron 6 of 8	1	NM_003730.6	ENSP00000426455.2		O00584-1
ENSG00000249141	ENST00000507747.1 link	c.386+279G>T		intron_variant	Intron 6 of 7	5		ENSP00000426906.1		H0YAE9

Frequencies

GnomAD3 genomes

AF:

0.110

AC:

16652

AN:

152028

Hom.:

1550

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0391

Gnomad AMI

AF:

0.0888

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.0811

Gnomad EAS

AF:

0.403

Gnomad SAS

AF:

0.308

Gnomad FIN

AF:

0.189

Gnomad MID

AF:

0.0886

Gnomad NFE

AF:

0.0851

Gnomad OTH

AF:

0.119

GnomAD2 exomes

AF:

0.176

AC:

42647

AN:

242290

AF XY:

0.174

show subpopulations

Gnomad AFR exome

AF:

0.0387

Gnomad AMR exome

AF:

0.305

Gnomad ASJ exome

AF:

0.0729

Gnomad EAS exome

AF:

0.418

Gnomad FIN exome

AF:

0.185

Gnomad NFE exome

AF:

0.0884

Gnomad OTH exome

AF:

0.140

GnomAD4 exome

AF:

0.149

AC:

79996

AN:

535540

Hom.:

9030

Cov.:

AF XY:

0.154

AC XY:

45496

AN XY:

294866

show subpopulations

African (AFR)

AF:

0.0383

AC:

598

AN:

15616

American (AMR)

AF:

0.295

AC:

12047

AN:

40794

Ashkenazi Jewish (ASJ)

AF:

0.0742

AC:

1340

AN:

18062

East Asian (EAS)

AF:

0.369

AC:

9942

AN:

26976

South Asian (SAS)

AF:

0.288

AC:

19593

AN:

68132

European-Finnish (FIN)

AF:

0.179

AC:

7602

AN:

42488

Middle Eastern (MID)

AF:

0.0855

AC:

316

AN:

3696

European-Non Finnish (NFE)

AF:

0.0854

AC:

24968

AN:

292308

Other (OTH)

AF:

0.131

AC:

3590

AN:

27468

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

3856

7711

11567

15422

19278

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

508

1016

1524

2032

2540

<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:

0.110

AC:

16676

AN:

152146

Hom.:

1552

Cov.:

AF XY:

0.120

AC XY:

8929

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0390

AC:

1622

AN:

41540

American (AMR)

AF:

0.200

AC:

3061

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0811

AC:

281

AN:

3466

East Asian (EAS)

AF:

0.402

AC:

2071

AN:

5158

South Asian (SAS)

AF:

0.310

AC:

1492

AN:

4818

European-Finnish (FIN)

AF:

0.189

AC:

1999

AN:

10580

Middle Eastern (MID)

AF:

0.0918

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0851

AC:

5782

AN:

67982

Other (OTH)

AF:

0.123

AC:

260

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

690

1379

2069

2758

3448

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

212

424

636

848

1060

<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:

0.0953

Hom.:

3338

Bravo

AF:

0.109

TwinsUK

AF:

0.0823

AC:

305

ALSPAC

AF:

0.0732

AC:

282

ESP6500AA

AF:

0.0428

AC:

ESP6500EA

AF:

0.0826

AC:

329

ExAC

AF:

0.167

AC:

19816

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.89

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.0

(source)

DANN

Benign

0.45

DEOGEN2

Benign

0.0095

Eigen

Benign

-0.67

Eigen_PC

Benign

-0.90

FATHMM_MKL

Benign

0.021

LIST_S2

Benign

0.17

MetaRNN

Benign

0.0034

MetaSVM

Benign

-1.0

PhyloP100

0.037

Sift4G

Uncertain

0.031

Vest4

0.34

ClinPred

0.00095

GERP RS

0.20

Mutation Taster

=100/0

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