Variant rs2071219 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000020.3(ACVRL1):c.314-35A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.443 in 1,579,214 control chromosomes in the GnomAD database, including 158,084 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16787 hom., cov: 32)

Exomes 𝑓: 0.44 ( 141297 hom. )

Consequence

ACVRL1
NM_000020.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: 0.227

Variant links:

Genes affected

ACVRL1 (HGNC:175): (activin A receptor like type 1) This gene encodes a type I cell-surface receptor for the TGF-beta superfamily of ligands. It shares with other type I receptors a high degree of similarity in serine-threonine kinase subdomains, a glycine- and serine-rich region (called the GS domain) preceding the kinase domain, and a short C-terminal tail. The encoded protein, sometimes termed ALK1, shares similar domain structures with other closely related ALK or activin receptor-like kinase proteins that form a subfamily of receptor serine/threonine kinases. Mutations in this gene are associated with hemorrhagic telangiectasia type 2, also known as Rendu-Osler-Weber syndrome 2. [provided by RefSeq, Jul 2008]

ACVRL1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 12-51913524-A-G is Benign according to our data. Variant chr12-51913524-A-G is described in ClinVar as [Benign]. Clinvar id is 254710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-51913524-A-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVRL1	NM_000020.3 linkuse as main transcript	c.314-35A>G		intron_variant		ENST00000388922.9	NP_000011.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVRL1	ENST00000388922.9 linkuse as main transcript	c.314-35A>G		intron_variant		1	NM_000020.3	ENSP00000373574	P1

Frequencies

GnomAD3 genomes

AF:

0.463

AC:

70261

AN:

151906

Hom.:

16775

Cov.:

show subpopulations

Gnomad AFR

AF:

0.555

Gnomad AMI

AF:

0.478

Gnomad AMR

AF:

0.330

Gnomad ASJ

AF:

0.484

Gnomad EAS

AF:

0.276

Gnomad SAS

AF:

0.468

Gnomad FIN

AF:

0.455

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.450

Gnomad OTH

AF:

0.440

GnomAD3 exomes

AF:

0.404

AC:

82874

AN:

204938

Hom.:

17797

AF XY:

0.415

AC XY:

46722

AN XY:

112590

show subpopulations

Gnomad AFR exome

AF:

0.551

Gnomad AMR exome

AF:

0.215

Gnomad ASJ exome

AF:

0.479

Gnomad EAS exome

AF:

0.285

Gnomad SAS exome

AF:

0.467

Gnomad FIN exome

AF:

0.443

Gnomad NFE exome

AF:

0.441

Gnomad OTH exome

AF:

0.421

GnomAD4 exome

AF:

0.441

AC:

629800

AN:

1427190

Hom.:

141297

Cov.:

AF XY:

0.443

AC XY:

314268

AN XY:

708856

show subpopulations

Gnomad4 AFR exome

AF:

0.563

Gnomad4 AMR exome

AF:

0.228

Gnomad4 ASJ exome

AF:

0.479

Gnomad4 EAS exome

AF:

0.265

Gnomad4 SAS exome

AF:

0.464

Gnomad4 FIN exome

AF:

0.440

Gnomad4 NFE exome

AF:

0.449

Gnomad4 OTH exome

AF:

0.444

GnomAD4 genome

AF:

0.463

AC:

70314

AN:

152024

Hom.:

16787

Cov.:

AF XY:

0.460

AC XY:

34146

AN XY:

74300

show subpopulations

Gnomad4 AFR

AF:

0.555

Gnomad4 AMR

AF:

0.329

Gnomad4 ASJ

AF:

0.484

Gnomad4 EAS

AF:

0.277

Gnomad4 SAS

AF:

0.468

Gnomad4 FIN

AF:

0.455

Gnomad4 NFE

AF:

0.450

Gnomad4 OTH

AF:

0.439

Alfa

AF:

0.458

Hom.:

3005

Bravo

AF:

0.451

Asia WGS

AF:

0.392

AC:

1365

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Telangiectasia, hereditary hemorrhagic, type 2

Benign:3

Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 13, 2022	- -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 14, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 22, 2024	- -

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	This variant is associated with the following publications: (PMID: 16179574, 16776339, 25847705) -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

7.5

DANN

Benign

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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