13-50909960-C-G

Variant names:

• chr13-50909960-C-G
• rs553446261
• NM_024570.4:c.-117C>G

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BS2_Supporting

The NM_024570.4(RNASEH2B):​c.-117C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00109 in 821,614 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00091 (0 hom., cov: 33)
  • Exomes 𝑓: 0.0011 (3 hom.)
• Consequence: RNASEH2B NM_024570.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.79
• 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: Benign. The variant received -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 13-50909960-C-G is Benign according to our data. Variant chr13-50909960-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 312326.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR geneVariant has number of homozygotes lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.-117C>G		5_prime_UTR	Exon 1 of 11	NP_078846.2	Q5TBB1-1
	RNASEH2B	NM_001411023.1		c.-117C>G		5_prime_UTR	Exon 1 of 11	NP_001397952.1	A0A2R8Y883
	RNASEH2B	NM_001142279.2		c.-117C>G		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.-117C>G		5_prime_UTR	Exon 1 of 11	ENSP00000337623.2	Q5TBB1-1
	RNASEH2B	ENST00000646960.1		c.-117C>G		5_prime_UTR	Exon 1 of 13	ENSP00000496481.1	A0A2R8Y7R8
	RNASEH2B	ENST00000951840.1		c.-117C>G		5_prime_UTR	Exon 1 of 11	ENSP00000621899.1

Frequencies

GnomAD3 genomes AF: 0.000907 AC: 138 AN: 152092 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.000507

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00118

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00137

Gnomad OTH AF: 0.00143

GnomAD4 exome AF: 0.00113 AC: 756 AN: 669412 Hom.: 3 Cov.: 9 AF XY: 0.00108 AC XY: 375 AN XY: 345944

African (AFR) AF: 0.000586 AC: 8 AN: 13646

American (AMR) AF: 0.000629 AC: 8 AN: 12714

Ashkenazi Jewish (ASJ) AF: 0.000129 AC: 2 AN: 15510

East Asian (EAS) AF: 0.00 AC: 0 AN: 24598

South Asian (SAS) AF: 0.000233 AC: 11 AN: 47284

European-Finnish (FIN) AF: 0.0000330 AC: 1 AN: 30284

Middle Eastern (MID) AF: 0.00203 AC: 5 AN: 2468

European-Non Finnish (NFE) AF: 0.00138 AC: 678 AN: 491044

Other (OTH) AF: 0.00135 AC: 43 AN: 31864

GnomAD4 genome AF: 0.000907 AC: 138 AN: 152202 Hom.: 0 Cov.: 33 AF XY: 0.000887 AC XY: 66 AN XY: 74416

African (AFR) AF: 0.000505 AC: 21 AN: 41556

American (AMR) AF: 0.00118 AC: 18 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00137 AC: 93 AN: 67980

Other (OTH) AF: 0.00142 AC: 3 AN: 2116

Alfa AF: 0.000794 Hom.: 0

Bravo AF: 0.00107

ClinVar

ClinVar submissions

Significance: Likely benign

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	8.9
DANN	Benign	0.84
PhyloP100		1.8
PromoterAI		-0.10	Neutral
Mutation Taster		=300/0	polymorphism

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: rs553446261; hg19: chr13-51484096;