Variant chr2-3547976-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -17 ACMG points: 0P and 17B. BP4_StrongBP6_Very_StrongBP7BS2

The NM_002936.6(RNASEH1):c.729C>T(p.Asp243=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00024 in 1,613,750 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00024 ( 2 hom. )

Consequence

RNASEH1
NM_002936.6 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.94

Variant links:

Genes affected

RNASEH1 (HGNC:18466): (ribonuclease H1) This gene encodes an endonuclease that specifically degrades the RNA of RNA-DNA hybrids and plays a key role in DNA replication and repair. Alternate in-frame start codon initiation results in the production of alternate isoforms that are directed to the mitochondria or to the nucleus. The production of the mitochondrial isoform is modulated by an upstream open reading frame (uORF). Mutations in this gene have been found in individuals with progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal recessive 2. Alternative splicing results in additional coding and non-coding transcript variants. Pseudogenes of this gene have been defined on chromosomes 2 and 17. [provided by RefSeq, Jul 2017]

RNASEH1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -17 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.51).

BP6

Variant 2-3547976-G-A is Benign according to our data. Variant chr2-3547976-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 735901.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=1.94 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RNASEH1	NM_002936.6 linkuse as main transcript	c.729C>T	p.Asp243=	synonymous_variant	7/8	ENST00000315212.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RNASEH1	ENST00000315212.4 linkuse as main transcript	c.729C>T	p.Asp243=	synonymous_variant	7/8	1	NM_002936.6	P1
RNASEH1	ENST00000436842.5 linkuse as main transcript	c.*835C>T		3_prime_UTR_variant, NMD_transcript_variant	7/8	2

Frequencies

GnomAD3 genomes

AF:

0.000243

AC:

AN:

151994

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.000194

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000412

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.000294

AC:

AN:

251466

Hom.:

AF XY:

0.000368

AC XY:

AN XY:

135904

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00119

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000359

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000404

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000239

AC:

350

AN:

1461640

Hom.:

Cov.:

AF XY:

0.000265

AC XY:

193

AN XY:

727134

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.0000671

Gnomad4 ASJ exome

AF:

0.000995

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000452

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000213

Gnomad4 OTH exome

AF:

0.000348

GnomAD4 genome

AF:

0.000243

AC:

AN:

152110

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74330

show subpopulations

Gnomad4 AFR

AF:

0.0000482

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.000194

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000412

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.000594

Hom.:

Bravo

AF:

0.000257

EpiCase

AF:

0.000382

EpiControl

AF:

0.000711

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 15, 2024	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Benign

0.79

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over