rs2071218

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000020.3(ACVRL1):c.313+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.435 in 1,608,936 control chromosomes in the GnomAD database, including 155,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16283 hom., cov: 31)

Exomes 𝑓: 0.43 ( 138856 hom. )

Consequence

ACVRL1
NM_000020.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.437

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

telangiectasia, hereditary hemorrhagic, type 2
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp
hereditary hemorrhagic telangiectasia
Inheritance: AR, AD Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet

ACVRL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 12-51913361-C-T is Benign according to our data. Variant chr12-51913361-C-T is described in ClinVar as Benign. ClinVar VariationId is 136293.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.544 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000020.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACVRL1	NM_000020.3	MANE Select	c.313+11C>T	intron	N/A	NP_000011.2	P37023
ACVRL1	NM_001077401.2		c.313+11C>T	intron	N/A	NP_001070869.1	A0A0S2Z310
ACVRL1	NM_001406487.1		c.313+11C>T	intron	N/A	NP_001393416.1	A0A0S2Z310

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
ACVRL1	ENST00000388922.9	TSL:1 MANE Select	c.313+11C>T	intron	N/A	ENSP00000373574.4	P37023
ACVRL1	ENST00000550683.5	TSL:1	c.355+11C>T	intron	N/A	ENSP00000447884.1	G3V1W8
ACVRL1	ENST00000551576.6	TSL:1	c.313+11C>T	intron	N/A	ENSP00000455848.2	P37023

Frequencies

GnomAD3 genomes

AF:

0.456

AC:

69152

AN:

151800

Hom.:

16274

Cov.:

show subpopulations

Gnomad AFR

AF:

0.550

Gnomad AMI

AF:

0.404

Gnomad AMR

AF:

0.320

Gnomad ASJ

AF:

0.483

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.467

Gnomad FIN

AF:

0.448

Gnomad MID

AF:

0.468

Gnomad NFE

AF:

0.442

Gnomad OTH

AF:

0.432

GnomAD2 exomes

AF:

0.404

AC:

97109

AN:

240616

AF XY:

0.413

show subpopulations

Gnomad AFR exome

AF:

0.548

Gnomad AMR exome

AF:

0.212

Gnomad ASJ exome

AF:

0.478

Gnomad EAS exome

AF:

0.282

Gnomad FIN exome

AF:

0.438

Gnomad NFE exome

AF:

0.433

Gnomad OTH exome

AF:

0.417

GnomAD4 exome

AF:

0.433

AC:

630481

AN:

1457018

Hom.:

138856

Cov.:

AF XY:

0.435

AC XY:

315085

AN XY:

724360

show subpopulations

African (AFR)

AF:

0.556

AC:

18568

AN:

33404

American (AMR)

AF:

0.224

AC:

9920

AN:

44346

Ashkenazi Jewish (ASJ)

AF:

0.478

AC:

12451

AN:

26040

East Asian (EAS)

AF:

0.265

AC:

10494

AN:

39612

South Asian (SAS)

AF:

0.463

AC:

39584

AN:

85472

European-Finnish (FIN)

AF:

0.437

AC:

22760

AN:

52088

Middle Eastern (MID)

AF:

0.441

AC:

2540

AN:

5756

European-Non Finnish (NFE)

AF:

0.439

AC:

487768

AN:

1110064

Other (OTH)

AF:

0.438

AC:

26396

AN:

60236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

23325

46650

69975

93300

116625

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14744

29488

44232

58976

73720

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.456

AC:

69203

AN:

151918

Hom.:

16283

Cov.:

AF XY:

0.453

AC XY:

33630

AN XY:

74266

show subpopulations

African (AFR)

AF:

0.550

AC:

22805

AN:

41454

American (AMR)

AF:

0.320

AC:

4888

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.483

AC:

1673

AN:

3466

East Asian (EAS)

AF:

0.275

AC:

1413

AN:

5144

South Asian (SAS)

AF:

0.467

AC:

2249

AN:

4816

European-Finnish (FIN)

AF:

0.448

AC:

4730

AN:

10560

Middle Eastern (MID)

AF:

0.476

AC:

140

AN:

294

European-Non Finnish (NFE)

AF:

0.442

AC:

30030

AN:

67886

Other (OTH)

AF:

0.431

AC:

907

AN:

2102

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1872

3744

5616

7488

9360

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

636

1272

1908

2544

3180

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.431

Hom.:

5183

Bravo

AF:

0.443

Asia WGS

AF:

0.390

AC:

1358

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Telangiectasia, hereditary hemorrhagic, type 2 (6)

not specified (5)

Cardiovascular phenotype (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

3.2

(source)

DANN

Benign

0.84

PhyloP100

-0.44

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over