rs864622702

chr12-51914374-TG-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_000020.3(ACVRL1):c.626-59del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0171 in 1,608,886 control chromosomes in the GnomAD database, including 258 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (12 hom., cov: 33)
  • Exomes 𝑓: 0.018 (246 hom.)
• Consequence: ACVRL1 NM_000020.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.07

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 12-51914374-TG-T is Benign according to our data. Variant chr12-51914374-TG-T is described in ClinVar as [Likely_benign]. Clinvar id is 220940.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0113 (1725/152226) while in subpopulation NFE AF= 0.0189 (1284/67980). AF 95% confidence interval is 0.018. There are 12 homozygotes in gnomad4. There are 750 alleles in male gnomad4 subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAd at 1726 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVRL1	NM_000020.3	c.626-59del		intron_variant		ENST00000388922.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVRL1	ENST00000388922.9	c.626-59del		intron_variant		1	NM_000020.3	P1

Frequencies

GnomAD3 genomes AF: 0.0113 AC: 1726 AN: 152108 Hom.: 12 Cov.: 33

Gnomad AFR AF: 0.00331

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00753

Gnomad ASJ AF: 0.0256

Gnomad EAS AF: 0.00424

Gnomad SAS AF: 0.00248

Gnomad FIN AF: 0.00358

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0189

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.0177 AC: 25733 AN: 1456660 Hom.: 246 AF XY: 0.0172 AC XY: 12436 AN XY: 724730

Gnomad4 AFR exome AF: 0.00261

Gnomad4 AMR exome AF: 0.00718

Gnomad4 ASJ exome AF: 0.0260

Gnomad4 EAS exome AF: 0.00212

Gnomad4 SAS exome AF: 0.00355

Gnomad4 FIN exome AF: 0.00602

Gnomad4 NFE exome AF: 0.0207

Gnomad4 OTH exome AF: 0.0167

GnomAD4 genome AF: 0.0113 AC: 1725 AN: 152226 Hom.: 12 Cov.: 33 AF XY: 0.0101 AC XY: 750 AN XY: 74432

Gnomad4 AFR AF: 0.00330

Gnomad4 AMR AF: 0.00752

Gnomad4 ASJ AF: 0.0256

Gnomad4 EAS AF: 0.00406

Gnomad4 SAS AF: 0.00249

Gnomad4 FIN AF: 0.00358

Gnomad4 NFE AF: 0.0189

Gnomad4 OTH AF: 0.00994

Alfa AF: 0.0154 Hom.: 2

Bravo AF: 0.0119

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Telangiectasia, hereditary hemorrhagic, type 2 Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 22, 2023

- -

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs864622702; hg19: chr12-52308158;