chr13-50909970-G-A

Variant names:

• chr13-50909970-G-A
• rs886050289
• NM_024570.4:c.-107G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024570.4(RNASEH2B):​c.-107G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000178 in 842,240 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000018 (1 hom.)
• Consequence: RNASEH2B NM_024570.4 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.186
• 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).

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.-107G>A		5_prime_UTR	Exon 1 of 11	NP_078846.2	Q5TBB1-1
	RNASEH2B	NM_001411023.1		c.-107G>A		5_prime_UTR	Exon 1 of 11	NP_001397952.1	A0A2R8Y883
	RNASEH2B	NM_001142279.2		c.-107G>A		5_prime_UTR	Exon 1 of 10	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.-107G>A		5_prime_UTR	Exon 1 of 11	ENSP00000337623.2	Q5TBB1-1
	RNASEH2B	ENST00000646960.1		c.-107G>A		5_prime_UTR	Exon 1 of 13	ENSP00000496481.1	A0A2R8Y7R8
	RNASEH2B	ENST00000951840.1		c.-107G>A		5_prime_UTR	Exon 1 of 11	ENSP00000621899.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000178 AC: 15 AN: 842240 Hom.: 1 Cov.: 11 AF XY: 0.00000935 AC XY: 4 AN XY: 427632

African (AFR) AF: 0.00 AC: 0 AN: 16910

American (AMR) AF: 0.00 AC: 0 AN: 14330

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 17188

East Asian (EAS) AF: 0.00 AC: 0 AN: 25410

South Asian (SAS) AF: 0.00 AC: 0 AN: 52942

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31000

Middle Eastern (MID) AF: 0.000349 AC: 1 AN: 2864

European-Non Finnish (NFE) AF: 0.0000217 AC: 14 AN: 643804

Other (OTH) AF: 0.00 AC: 0 AN: 37792

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Aicardi-Goutieres syndrome 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.2
DANN	Benign	0.95
PhyloP100		-0.19
PromoterAI		-0.033	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: rs886050289; hg19: chr13-51484106;