chr13-50956394-G-T

Position:

chr13-50956394-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_024570.4(RNASEH2B):c.859G>T(p.Ala287Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00147 in 1,603,568 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0017 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 16 hom. )

Consequence

RNASEH2B
NM_024570.4 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 5.46

Variant links:

Genes affected

RNASEH2B (HGNC:25671): (ribonuclease H2 subunit B) RNase H2 is composed of a single catalytic subunit (A) and two non-catalytic subunits (B and C) and specifically degrades the RNA of RNA:DNA hybrids. The protein encoded by this gene is the non-catalytic B subunit of RNase H2, which is thought to play a role in DNA replication. Multiple transcript variants encoding different isoforms have been found for this gene. Defects in this gene are a cause of Aicardi-Goutieres syndrome type 2 (AGS2). [provided by RefSeq, Nov 2008]

RNASEH2B links:

RNASEH2B (HGNC:):

RNASEH2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0097846985).

BP6

Variant 13-50956394-G-T is Benign according to our data. Variant chr13-50956394-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 312334.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr13-50956394-G-T is described in Lovd as [Likely_pathogenic]. Variant chr13-50956394-G-T is described in Lovd as [Likely_benign]. Variant chr13-50956394-G-T is described in Lovd as [Benign].

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0017 (259/152154) while in subpopulation EAS AF= 0.0211 (109/5172). AF 95% confidence interval is 0.0179. There are 2 homozygotes in gnomad4. There are 145 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RNASEH2B	NM_024570.4 linkuse as main transcript	c.859G>T	p.Ala287Ser	missense_variant	11/11	ENST00000336617.8	NP_078846.2	Q5TBB1-1Q8N451

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RNASEH2B	ENST00000336617.8 linkuse as main transcript	c.859G>T	p.Ala287Ser	missense_variant	11/11	1	NM_024570.4	ENSP00000337623.2		Q5TBB1-1

Frequencies

GnomAD3 genomes

AF:

0.00170

AC:

259

AN:

152038

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00400

Gnomad ASJ

AF:

0.000289

Gnomad EAS

AF:

0.0210

Gnomad SAS

AF:

0.00166

Gnomad FIN

AF:

0.000945

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000882

Gnomad OTH

AF:

0.00144

GnomAD3 exomes

AF:

0.00445

AC:

1054

AN:

236908

Hom.:

AF XY:

0.00393

AC XY:

503

AN XY:

127972

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0144

Gnomad ASJ exome

AF:

0.000209

Gnomad EAS exome

AF:

0.0214

Gnomad SAS exome

AF:

0.00119

Gnomad FIN exome

AF:

0.00137

Gnomad NFE exome

AF:

0.00101

Gnomad OTH exome

AF:

0.00188

GnomAD4 exome

AF:

0.00144

AC:

2097

AN:

1451414

Hom.:

Cov.:

AF XY:

0.00140

AC XY:

1007

AN XY:

721350

show subpopulations

Gnomad4 AFR exome

AF:

0.0000602

Gnomad4 AMR exome

AF:

0.0128

Gnomad4 ASJ exome

AF:

0.000155

Gnomad4 EAS exome

AF:

0.0187

Gnomad4 SAS exome

AF:

0.00149

Gnomad4 FIN exome

AF:

0.00114

Gnomad4 NFE exome

AF:

0.000451

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.00170

AC:

259

AN:

152154

Hom.:

Cov.:

AF XY:

0.00195

AC XY:

145

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.00399

Gnomad4 ASJ

AF:

0.000289

Gnomad4 EAS

AF:

0.0211

Gnomad4 SAS

AF:

0.00166

Gnomad4 FIN

AF:

0.000945

Gnomad4 NFE

AF:

0.000882

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00176

Hom.:

Bravo

AF:

0.00242

ESP6500AA

AF:

0.000455

AC:

ESP6500EA

AF:

0.000582

AC:

ExAC

AF:

0.00375

AC:

455

Asia WGS

AF:

0.00895

AC:

AN:

3476

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Nov 04, 2016	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Oct 01, 2023	RNASEH2B: BS1, BS2 -

Aicardi-Goutieres syndrome 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Sep 29, 2021	- -

not specified

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	Jan 18, 2024	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.059

BayesDel_noAF

Pathogenic

0.16

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.53

D;.;.;.;.;.;.;.;T;T

Eigen

Uncertain

0.66

Eigen_PC

Pathogenic

0.69

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.85

T;T;D;T;D;T;D;T;.;D

MetaRNN

Benign

0.0098

T;T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

0.58

MutationAssessor

Uncertain

2.3

M;.;.;.;.;.;.;.;.;.

PrimateAI

Uncertain

0.60

PROVEAN

Benign

-1.0

N;.;.;.;.;.;.;.;.;.

REVEL

Uncertain

0.59

Sift

Benign

0.23

T;.;.;.;.;.;.;.;.;.

Sift4G

Benign

0.19

T;.;.;.;.;.;.;.;.;.

Polyphen

0.96

D;.;.;.;.;.;.;.;.;.

Vest4

0.22

MVP

0.96

MPC

0.16

ClinPred

0.050

GERP RS

6.1

Varity_R

0.16

gMVP

0.34

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over