rs116205353

Variant names:

• chr13-50909575-A-G
• rs116205353
• ENST00000454605.5:n.282+908T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The ENST00000454605.5(RNASEH2B-AS1):​n.282+908T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.017 in 152,792 control chromosomes in the GnomAD database, including 73 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.017 (73 hom., cov: 32)
  • Exomes 𝑓: 0.0066 (0 hom.)
• Consequence: RNASEH2B-AS1 ENST00000454605.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.882
• Publications: 0 publications found

Genes affected

RNASEH2B-AS1 (HGNC:39967): (RNASEH2B antisense RNA 1)

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 Gene-Disease associations (from GenCC):

• Aicardi-Goutieres syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• RNASEH2B-related type 1 interferonopathy

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• Aicardi-Goutieres syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• prostate cancer

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 13-50909575-A-G is Benign according to our data. Variant chr13-50909575-A-G is described in ClinVar as Benign. ClinVar VariationId is 1221632.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0576 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000454605.5. 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-AS1	NR_046552.1		n.230+908T>C		intron	N/A
	RNASEH2B	NM_024570.4	MANE Select	c.-502A>G		upstream_gene	N/A	NP_078846.2	Q5TBB1-1
	RNASEH2B	NM_001411023.1		c.-502A>G		upstream_gene	N/A	NP_001397952.1	A0A2R8Y883

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RNASEH2B-AS1	ENST00000454605.5	TSL:3	n.282+908T>C		intron	N/A
	RNASEH2B-AS1	ENST00000593750.5	TSL:5	n.112+908T>C		intron	N/A
	RNASEH2B-AS1	ENST00000594244.1	TSL:5	n.112+908T>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0170 AC: 2587 AN: 152220 Hom.: 74 Cov.: 32

Gnomad AFR AF: 0.0596

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00549

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.0129

GnomAD4 exome AF: 0.00661 AC: 3 AN: 454 Hom.: 0 AF XY: 0.0101 AC XY: 3 AN XY: 298

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.188 AC: 3 AN: 16

American (AMR) AF: 0.00 AC: 0 AN: 6

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AF: 0.00 AC: 0 AN: 122

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 270

Other (OTH) AF: 0.00 AC: 0 AN: 20

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.0338994), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.0170 AC: 2594 AN: 152338 Hom.: 73 Cov.: 32 AF XY: 0.0158 AC XY: 1179 AN XY: 74504

African (AFR) AF: 0.0596 AC: 2477 AN: 41578

American (AMR) AF: 0.00549 AC: 84 AN: 15310

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5170

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68026

Other (OTH) AF: 0.0128 AC: 27 AN: 2116

Alfa AF: 0.00797 Hom.: 12

Bravo AF: 0.0186

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.7
DANN	Benign	0.49
PhyloP100		-0.88
PromoterAI		0.0028	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs116205353; hg19: chr13-51483711;