rs900876937

Variant names:

• chr13-50910116-C-A
• rs900876937
• NM_024570.4:c.40C>A

Your query was ambiguous. Multiple possible variants found:

• chr13-50910116-C-A
• chr13-50910116-C-G
• chr13-50910116-C-T

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 2P and 3B. PM2 BP4_Moderate BP7

The NM_024570.4(RNASEH2B):​c.40C>A​(p.Arg14Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000153 in 1,306,918 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000015 (0 hom.)
• Consequence: RNASEH2B NM_024570.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.153
• Publications: 0 publications found

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-AS1 (HGNC:39967): (RNASEH2B antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).
• BP7: Synonymous conserved (PhyloP=-0.153 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024570.4. 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
	RNASEH2B	NM_024570.4	MANE Select	c.40C>A	p.Arg14Arg	synonymous	Exon 1 of 11	NP_078846.2
	RNASEH2B	NM_001411023.1		c.40C>A	p.Arg14Arg	synonymous	Exon 1 of 11	NP_001397952.1
	RNASEH2B	NM_001142279.2		c.40C>A	p.Arg14Arg	synonymous	Exon 1 of 10	NP_001135751.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEH2B	ENST00000336617.8	TSL:1 MANE Select	c.40C>A	p.Arg14Arg	synonymous	Exon 1 of 11	ENSP00000337623.2
	RNASEH2B	ENST00000646960.1		c.40C>A	p.Arg14Arg	synonymous	Exon 1 of 13	ENSP00000496481.1
	RNASEH2B	ENST00000642721.1		c.40C>A	p.Arg14Arg	synonymous	Exon 1 of 12	ENSP00000495650.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000153 AC: 2 AN: 1306918 Hom.: 0 Cov.: 31 AF XY: 0.00000311 AC XY: 2 AN XY: 642356

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 26078

American (AMR) AF: 0.0000438 AC: 1 AN: 22816

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22100

East Asian (EAS) AF: 0.00 AC: 0 AN: 28164

South Asian (SAS) AF: 0.0000145 AC: 1 AN: 68754

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 41800

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3996

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1039460

Other (OTH) AF: 0.00 AC: 0 AN: 53750

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	12
DANN	Benign	0.97
PhyloP100		-0.15
PromoterAI		-0.054	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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

Other links and lift over

dbSNP: rs900876937; hg19: chr13-51484252;