chr13-50922184-G-A

Position:

• chr13-50922184-G-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNASEH2B	NM_024570.4	c.65-5223G>A		intron_variant		ENST00000336617.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASEH2B	ENST00000336617.8	c.65-5223G>A		intron_variant		1	NM_024570.4	P3

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

Gnomad4 AFR AF: 0.712

Gnomad4 AMR AF: 0.619

Gnomad4 ASJ AF: 0.568

Gnomad4 EAS AF: 0.435

Gnomad4 SAS AF: 0.348

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.600

Gnomad4 OTH AF: 0.606

Alfa AF: 0.621 Hom.: 4694

Bravo AF: 0.625

Asia WGS AF: 0.415 AC: 1445 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	5.3
DANN	Benign	0.36

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

Other links and lift over

dbSNP: rs7988945; hg19: chr13-51496320;