rs11169974

chr12-51996512-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_004302.5(ACVR1B):c.*2402C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0276 in 152,746 control chromosomes in the GnomAD database, including 66 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 0.028 (66 hom., cov: 32)
  • Exomes 𝑓: 0.021 (0 hom.)
• Consequence: ACVR1B NM_004302.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79

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=-0.81).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0276 (4199/152260) while in subpopulation AFR AF= 0.0387 (1608/41534). AF 95% confidence interval is 0.0371. There are 66 homozygotes in gnomad4. There are 2080 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 4203 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ACVR1B	NM_004302.5	c.*2402C>T		3_prime_UTR_variant	9/9	ENST00000257963.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ACVR1B	ENST00000257963.9	c.*2402C>T		3_prime_UTR_variant	9/9	1	NM_004302.5	P1

Frequencies

GnomAD3 genomes AF: 0.0276 AC: 4203 AN: 152142 Hom.: 66 Cov.: 32

Gnomad AFR AF: 0.0389

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0238

Gnomad ASJ AF: 0.0130

Gnomad EAS AF: 0.00673

Gnomad SAS AF: 0.0290

Gnomad FIN AF: 0.0333

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0232

Gnomad OTH AF: 0.0263

GnomAD4 exome AF: 0.0206 AC: 10 AN: 486 Hom.: 0 Cov.: 0 AF XY: 0.0208 AC XY: 6 AN XY: 288

Gnomad4 FIN exome AF: 0.0215

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0276 AC: 4199 AN: 152260 Hom.: 66 Cov.: 32 AF XY: 0.0279 AC XY: 2080 AN XY: 74446

Gnomad4 AFR AF: 0.0387

Gnomad4 AMR AF: 0.0238

Gnomad4 ASJ AF: 0.0130

Gnomad4 EAS AF: 0.00675

Gnomad4 SAS AF: 0.0290

Gnomad4 FIN AF: 0.0333

Gnomad4 NFE AF: 0.0232

Gnomad4 OTH AF: 0.0256

Alfa AF: 0.0242 Hom.: 8

Bravo AF: 0.0265

Asia WGS AF: 0.0190 AC: 65 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	4.4
Dann	Benign	0.75
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs11169974; hg19: chr12-52390296;