13-50909932-G-T

Variant names:

• chr13-50909932-G-T
• rs1227696445
• NM_024570.4:c.-145G>T

Variant summary

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

The NM_024570.4(RNASEH2B):​c.-145G>T variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RNASEH2B NM_024570.4 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0920
• 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=-0.78).

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.-145G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_078846.2	Q5TBB1-1
	RNASEH2B	NM_024570.4	MANE Select	c.-145G>T		5_prime_UTR	Exon 1 of 11	NP_078846.2	Q5TBB1-1
	RNASEH2B	NM_001411023.1		c.-145G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	NP_001397952.1	A0A2R8Y883

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEH2B	ENST00000336617.8	TSL:1 MANE Select	c.-145G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 11	ENSP00000337623.2	Q5TBB1-1
	RNASEH2B	ENST00000336617.8	TSL:1 MANE Select	c.-145G>T		5_prime_UTR	Exon 1 of 11	ENSP00000337623.2	Q5TBB1-1
	RNASEH2B	ENST00000646960.1		c.-145G>T		5_prime_UTR_premature_start_codon_gain	Exon 1 of 13	ENSP00000496481.1	A0A2R8Y7R8

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 411172 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 218268

African (AFR) AF: 0.00 AC: 0 AN: 8500

American (AMR) AF: 0.00 AC: 0 AN: 8072

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 11748

East Asian (EAS) AF: 0.00 AC: 0 AN: 23192

South Asian (SAS) AF: 0.00 AC: 0 AN: 34022

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 27714

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1782

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 273762

Other (OTH) AF: 0.00 AC: 0 AN: 22380

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.092
PromoterAI		-0.051	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1227696445; hg19: chr13-51484068;