chr12-51995107-A-G

Position:

• chr12-51995107-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000257963.9(ACVR1B):​c.*997A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.337 in 152,986 control chromosomes in the GnomAD database, including 9,546 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 0.34 (9508 hom., cov: 31)
  • Exomes 𝑓: 0.27 (38 hom.)
• Consequence: ACVR1B ENST00000257963.9 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.29

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1B	NM_004302.5	c.*997A>G		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.*997A>G		3_prime_UTR_variant	9/9	1	NM_004302.5	ENSP00000257963	P1

Frequencies

GnomAD3 genomes AF: 0.337 AC: 51243 AN: 151884 Hom.: 9479 Cov.: 31

Gnomad AFR AF: 0.441

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.322

Gnomad SAS AF: 0.269

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.344

GnomAD4 exome AF: 0.274 AC: 270 AN: 984 Hom.: 38 Cov.: 0 AF XY: 0.285 AC XY: 151 AN XY: 530

Gnomad4 AFR exome AF: 0.250

Gnomad4 AMR exome AF: 0.250

Gnomad4 ASJ exome AF: 0.250

Gnomad4 EAS exome AF: 0.393

Gnomad4 SAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.252

Gnomad4 OTH exome AF: 0.269

GnomAD4 genome AF: 0.338 AC: 51314 AN: 152002 Hom.: 9508 Cov.: 31 AF XY: 0.340 AC XY: 25227 AN XY: 74290

Gnomad4 AFR AF: 0.441

Gnomad4 AMR AF: 0.507

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.324

Gnomad4 SAS AF: 0.268

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.339

Alfa AF: 0.279 Hom.: 6496

Bravo AF: 0.368

Asia WGS AF: 0.349 AC: 1212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.050
DANN	Benign	0.65
RBP_binding_hub_radar		0.97
RBP_regulation_power_radar		2.2

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: rs2854464; hg19: chr12-52388891; COSMIC: COSV57779149; COSMIC: COSV57779149;