ENST00000646960.1:c.-294C>T

Variant names:

• chr13-50909783-C-T
• rs1879223150
• ENST00000646960.1:c.-294C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000646960.1(RNASEH2B):​c.-294C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNASEH2B ENST00000646960.1 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.76
• 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 -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000646960.1. 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_001142279.2		c.-294C>T		5_prime_UTR	Exon 1 of 10	NP_001135751.1	Q5TBB1-2
	RNASEH2B-AS1	NR_046552.1		n.230+700G>A		intron	N/A
	RNASEH2B	NM_024570.4	MANE Select	c.-294C>T		upstream_gene	N/A	NP_078846.2	Q5TBB1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEH2B	ENST00000646960.1		c.-294C>T		5_prime_UTR	Exon 1 of 13	ENSP00000496481.1	A0A2R8Y7R8
	RNASEH2B	ENST00000951840.1		c.-294C>T		5_prime_UTR	Exon 1 of 11	ENSP00000621899.1
	RNASEH2B	ENST00000951841.1		c.-294C>T		5_prime_UTR	Exon 1 of 11	ENSP00000621900.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 175486 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 91908

African (AFR) AF: 0.00 AC: 0 AN: 4238

American (AMR) AF: 0.00 AC: 0 AN: 3648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 6232

East Asian (EAS) AF: 0.00 AC: 0 AN: 12666

South Asian (SAS) AF: 0.00 AC: 0 AN: 14318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 12318

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 884

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 110184

Other (OTH) AF: 0.00 AC: 0 AN: 10998

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

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	-0.65
CADD	Benign	15
DANN	Benign	0.95
PhyloP100		1.8
PromoterAI		0.049	Neutral

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: rs1879223150; hg19: chr13-51483919;