chr12-51912005-A-G

Position:

• chr12-51912005-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_000020.3(ACVRL1):​c.-5-465A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.322 in 151,950 control chromosomes in the GnomAD database, including 8,190 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.32 (8190 hom., cov: 31)
• Consequence: ACVRL1 NM_000020.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.92

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 12-51912005-A-G is Benign according to our data. Variant chr12-51912005-A-G is described in ClinVar as [Benign]. Clinvar id is 1174347.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.547 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVRL1	NM_000020.3	c.-5-465A>G		intron_variant		ENST00000388922.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVRL1	ENST00000388922.9	c.-5-465A>G		intron_variant		1	NM_000020.3	P1
ACVRL1	ENST00000551576.6	c.-5-465A>G		intron_variant		1		P1
ACVRL1	ENST00000552678.2	c.-5-465A>G		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.322 AC: 48891 AN: 151830 Hom.: 8181 Cov.: 31

Gnomad AFR AF: 0.371

Gnomad AMI AF: 0.204

Gnomad AMR AF: 0.270

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.565

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.328

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.284

Gnomad OTH AF: 0.319

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.322 AC: 48931 AN: 151950 Hom.: 8190 Cov.: 31 AF XY: 0.323 AC XY: 23942 AN XY: 74236

Gnomad4 AFR AF: 0.371

Gnomad4 AMR AF: 0.270

Gnomad4 ASJ AF: 0.329

Gnomad4 EAS AF: 0.564

Gnomad4 SAS AF: 0.359

Gnomad4 FIN AF: 0.328

Gnomad4 NFE AF: 0.284

Gnomad4 OTH AF: 0.324

Alfa AF: 0.312 Hom.: 991

Bravo AF: 0.321

Asia WGS AF: 0.462 AC: 1605 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	17
DANN	Benign	0.87

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: rs1690215; hg19: chr12-52305789;