rs7988945

Variant names:

• chr13-50922184-G-A
• rs7988945
• NM_024570.4:c.65-5223G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024570.4(RNASEH2B):​c.65-5223G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.618 in 152,080 control chromosomes in the GnomAD database, including 29,598 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 0.62 (29598 hom., cov: 32)
• Consequence: RNASEH2B NM_024570.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.558
• Publications: 6 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 Gene-Disease associations (from GenCC):

• Aicardi-Goutieres syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• RNASEH2B-related type 1 interferonopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Aicardi-Goutieres syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.705 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEH2B	NM_024570.4	MANE Select	c.65-5223G>A		intron	N/A	NP_078846.2	Q5TBB1-1
	RNASEH2B	NM_001411023.1		c.65-5223G>A		intron	N/A	NP_001397952.1	A0A2R8Y883
	RNASEH2B	NM_001142279.2		c.65-5223G>A		intron	N/A	NP_001135751.1	Q5TBB1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEH2B	ENST00000336617.8	TSL:1 MANE Select	c.65-5223G>A		intron	N/A	ENSP00000337623.2	Q5TBB1-1
	RNASEH2B	ENST00000646960.1		c.65-5223G>A		intron	N/A	ENSP00000496481.1	A0A2R8Y7R8
	RNASEH2B	ENST00000643159.1		c.-27+853G>A		intron	N/A	ENSP00000495587.1	A0A2R8YEH2

Frequencies

GnomAD3 genomes AF: 0.618 AC: 93860 AN: 151960 Hom.: 29550 Cov.: 32

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.512

Gnomad AMR AF: 0.619

Gnomad ASJ AF: 0.568

Gnomad EAS AF: 0.435

Gnomad SAS AF: 0.348

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.582

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.606

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.618 AC: 93971 AN: 152080 Hom.: 29598 Cov.: 32 AF XY: 0.614 AC XY: 45671 AN XY: 74330

African (AFR) AF: 0.712 AC: 29500 AN: 41454

American (AMR) AF: 0.619 AC: 9460 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.568 AC: 1971 AN: 3468

East Asian (EAS) AF: 0.435 AC: 2252 AN: 5172

South Asian (SAS) AF: 0.348 AC: 1679 AN: 4822

European-Finnish (FIN) AF: 0.603 AC: 6381 AN: 10574

Middle Eastern (MID) AF: 0.575 AC: 169 AN: 294

European-Non Finnish (NFE) AF: 0.600 AC: 40813 AN: 67992

Other (OTH) AF: 0.606 AC: 1279 AN: 2112

Alfa AF: 0.623 Hom.: 4881

Bravo AF: 0.625

Asia WGS AF: 0.415 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.3
DANN	Benign	0.36
PhyloP100		0.56
Mutation Taster		=100/0	polymorphism (auto)

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: rs7988945; hg19: chr13-51496320;