NM_000020.3:c.1377+45T>C

Variant names:

Variant summary

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

The NM_000020.3(ACVRL1):c.1377+45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 1,612,628 control chromosomes in the GnomAD database, including 56,825 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.31 ( 8354 hom., cov: 32)

Exomes 𝑓: 0.25 ( 48471 hom. )

Consequence

ACVRL1
NM_000020.3 intron

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.824

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=-0.85).

BP6

Variant 12-51919160-T-C is Benign according to our data. Variant chr12-51919160-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 254709.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-51919160-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.485 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVRL1	NM_000020.3 link	c.1377+45T>C		intron_variant	Intron 9 of 9	ENST00000388922.9	NP_000011.2	P37023A0A0S2Z310

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVRL1	ENST00000388922.9 link	c.1377+45T>C		intron_variant	Intron 9 of 9	1	NM_000020.3	ENSP00000373574.4		P37023

Frequencies

GnomAD3 genomes

AF:

0.312

AC:

47310

AN:

151594

Hom.:

8333

Cov.:

show subpopulations

Gnomad AFR

AF:

0.491

Gnomad AMI

AF:

0.192

Gnomad AMR

AF:

0.225

Gnomad ASJ

AF:

0.279

Gnomad EAS

AF:

0.451

Gnomad SAS

AF:

0.234

Gnomad FIN

AF:

0.219

Gnomad MID

AF:

0.266

Gnomad NFE

AF:

0.237

Gnomad OTH

AF:

0.295

GnomAD3 exomes

AF:

0.264

AC:

65716

AN:

248984

Hom.:

9332

AF XY:

0.258

AC XY:

34723

AN XY:

134746

show subpopulations

Gnomad AFR exome

AF:

0.496

Gnomad AMR exome

AF:

0.190

Gnomad ASJ exome

AF:

0.284

Gnomad EAS exome

AF:

0.423

Gnomad SAS exome

AF:

0.232

Gnomad FIN exome

AF:

0.233

Gnomad NFE exome

AF:

0.241

Gnomad OTH exome

AF:

0.253

GnomAD4 exome

AF:

0.252

AC:

367933

AN:

1460916

Hom.:

48471

Cov.:

AF XY:

0.251

AC XY:

182227

AN XY:

726724

show subpopulations

Gnomad4 AFR exome

AF:

0.501

Gnomad4 AMR exome

AF:

0.191

Gnomad4 ASJ exome

AF:

0.288

Gnomad4 EAS exome

AF:

0.436

Gnomad4 SAS exome

AF:

0.237

Gnomad4 FIN exome

AF:

0.237

Gnomad4 NFE exome

AF:

0.240

Gnomad4 OTH exome

AF:

0.271

GnomAD4 genome

AF:

0.312

AC:

47370

AN:

151712

Hom.:

8354

Cov.:

AF XY:

0.309

AC XY:

22872

AN XY:

74122

show subpopulations

Gnomad4 AFR

AF:

0.491

Gnomad4 AMR

AF:

0.224

Gnomad4 ASJ

AF:

0.279

Gnomad4 EAS

AF:

0.451

Gnomad4 SAS

AF:

0.234

Gnomad4 FIN

AF:

0.219

Gnomad4 NFE

AF:

0.237

Gnomad4 OTH

AF:

0.299

Alfa

AF:

0.263

Hom.:

1462

Bravo

AF:

0.322

Asia WGS

AF:

0.346

AC:

1200

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Telangiectasia, hereditary hemorrhagic, type 2

Benign:2

Nov 27, 2024

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 05, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 16, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

3.4

DANN

Benign

0.39

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