rs2714

Positions:

• chr12-51995500-C-A
• chr12-51995500-C-T

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_004302.5(ACVR1B):​c.*1390C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00495 in 152,544 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0050 (5 hom., cov: 31)
  • Exomes 𝑓: 0.0046 (0 hom.)
• Consequence: ACVR1B NM_004302.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.81

Genes affected

ACVR1B (HGNC:172): (activin A receptor type 1B) This gene encodes an activin A type IB receptor. Activins are dimeric growth and differentiation factors which belong to the transforming growth factor-beta (TGF-beta) superfamily of structurally related signaling proteins. Activins signal through a heteromeric complex of receptor serine kinases which include at least two type I and two type II receptors. This protein is a type I receptor which is essential for signaling. Mutations in this gene are associated with pituitary tumors. Alternate splicing results in multiple transcript variants.[provided by RefSeq, Jun 2010]

ACMG classification

Verdict is Likely_benign. Variant got -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BS2: High AC in GnomAd4 at 753 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1B	NM_004302.5	c.*1390C>A		3_prime_UTR_variant	9/9	ENST00000257963.9	NP_004293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1B	ENST00000257963.9	c.*1390C>A		3_prime_UTR_variant	9/9	1	NM_004302.5	ENSP00000257963	P1

Frequencies

GnomAD3 genomes AF: 0.00495 AC: 753 AN: 151988 Hom.: 5 Cov.: 31

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.0910

Gnomad AMR AF: 0.00609

Gnomad ASJ AF: 0.000866

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00236

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00699

Gnomad OTH AF: 0.00672

GnomAD4 exome AF: 0.00459 AC: 2 AN: 436 Hom.: 0 Cov.: 0 AF XY: 0.00379 AC XY: 1 AN XY: 264

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00469

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00495 AC: 753 AN: 152108 Hom.: 5 Cov.: 31 AF XY: 0.00460 AC XY: 342 AN XY: 74360

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00609

Gnomad4 ASJ AF: 0.000866

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.00236

Gnomad4 NFE AF: 0.00700

Gnomad4 OTH AF: 0.00665

Alfa AF: 0.00377 Hom.: 0

Bravo AF: 0.00539

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.81

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: rs2714; hg19: chr12-52389284;