chr13-50909965-C-T

Variant names:

• chr13-50909965-C-T
• rs184573722
• NM_024570.4:c.-112C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_024570.4(RNASEH2B):​c.-112C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 906,980 control chromosomes in the GnomAD database, including 47 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0065 (12 hom., cov: 33)
  • Exomes 𝑓: 0.0058 (35 hom.)
• Consequence: RNASEH2B NM_024570.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.213
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BP6: Variant 13-50909965-C-T is Benign according to our data. Variant chr13-50909965-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 312327.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00649 (988/152260) while in subpopulation NFE AF = 0.00572 (389/67982). AF 95% confidence interval is 0.00525. There are 12 homozygotes in GnomAd4. There are 613 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 12 AD,AR gene

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.-112C>T		5_prime_UTR	Exon 1 of 11	NP_078846.2	Q5TBB1-1
	RNASEH2B	NM_001411023.1		c.-112C>T		5_prime_UTR	Exon 1 of 11	NP_001397952.1	A0A2R8Y883
	RNASEH2B	NM_001142279.2		c.-112C>T		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.-112C>T		5_prime_UTR	Exon 1 of 11	ENSP00000337623.2	Q5TBB1-1
	RNASEH2B	ENST00000646960.1		c.-112C>T		5_prime_UTR	Exon 1 of 13	ENSP00000496481.1	A0A2R8Y7R8
	RNASEH2B	ENST00000951840.1		c.-112C>T		5_prime_UTR	Exon 1 of 11	ENSP00000621899.1

Frequencies

GnomAD3 genomes AF: 0.00649 AC: 988 AN: 152152 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.000892

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000851

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0508

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00572

Gnomad OTH AF: 0.00191

GnomAD4 exome AF: 0.00578 AC: 4363 AN: 754720 Hom.: 35 Cov.: 10 AF XY: 0.00555 AC XY: 2145 AN XY: 386780

African (AFR) AF: 0.000523 AC: 8 AN: 15292

American (AMR) AF: 0.000582 AC: 8 AN: 13750

Ashkenazi Jewish (ASJ) AF: 0.00152 AC: 25 AN: 16482

East Asian (EAS) AF: 0.00 AC: 0 AN: 24992

South Asian (SAS) AF: 0.00 AC: 0 AN: 50602

European-Finnish (FIN) AF: 0.0328 AC: 1008 AN: 30740

Middle Eastern (MID) AF: 0.000371 AC: 1 AN: 2696

European-Non Finnish (NFE) AF: 0.00564 AC: 3188 AN: 565310

Other (OTH) AF: 0.00359 AC: 125 AN: 34856

GnomAD4 genome AF: 0.00649 AC: 988 AN: 152260 Hom.: 12 Cov.: 33 AF XY: 0.00823 AC XY: 613 AN XY: 74450

African (AFR) AF: 0.000890 AC: 37 AN: 41576

American (AMR) AF: 0.000849 AC: 13 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00173 AC: 6 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.0508 AC: 539 AN: 10608

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

European-Non Finnish (NFE) AF: 0.00572 AC: 389 AN: 67982

Other (OTH) AF: 0.00189 AC: 4 AN: 2116

Alfa AF: 0.00371 Hom.: 0

Bravo AF: 0.00271

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Aicardi-Goutieres syndrome 2 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	7.6
DANN	Benign	0.93
PhyloP100		0.21
PromoterAI		-0.019	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs184573722; hg19: chr13-51484101;