rs34050429

Positions:

• chr12-51987114-G-A

Variant summary

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

The NM_004302.5(ACVR1B):​c.1261+172G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00922 in 867,400 control chromosomes in the GnomAD database, including 458 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 0.034 (297 hom., cov: 33)
  • Exomes 𝑓: 0.0040 (161 hom.)
• Consequence: ACVR1B NM_004302.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.519

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 (MetaRNN=0.0019359291).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.116 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
ACVR1B	NM_004302.5	c.1261+172G>A		intron_variant		ENST00000257963.9	NP_004293.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ACVR1B	ENST00000257963.9	c.1261+172G>A		intron_variant		1	NM_004302.5	ENSP00000257963	P1

Frequencies

GnomAD3 genomes AF: 0.0340 AC: 5167 AN: 152120 Hom.: 298 Cov.: 33

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0115

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0273

GnomAD3 exomes AF: 0.00853 AC: 1441 AN: 168866 Hom.: 95 AF XY: 0.00619 AC XY: 558 AN XY: 90086

Gnomad AFR exome AF: 0.133

Gnomad AMR exome AF: 0.00408

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000244

Gnomad FIN exome AF: 0.000304

Gnomad NFE exome AF: 0.000269

Gnomad OTH exome AF: 0.00491

GnomAD4 exome AF: 0.00396 AC: 2832 AN: 715162 Hom.: 161 Cov.: 9 AF XY: 0.00307 AC XY: 1161 AN XY: 378510

Gnomad4 AFR exome AF: 0.120

Gnomad4 AMR exome AF: 0.00532

Gnomad4 ASJ exome AF: 0.0000953

Gnomad4 EAS exome AF: 0.0000296

Gnomad4 SAS exome AF: 0.000281

Gnomad4 FIN exome AF: 0.000179

Gnomad4 NFE exome AF: 0.000185

Gnomad4 OTH exome AF: 0.00801

GnomAD4 genome AF: 0.0339 AC: 5167 AN: 152238 Hom.: 297 Cov.: 33 AF XY: 0.0327 AC XY: 2431 AN XY: 74444

Gnomad4 AFR AF: 0.118

Gnomad4 AMR AF: 0.0115

Gnomad4 ASJ AF: 0.000576

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000250

Gnomad4 OTH AF: 0.0270

Alfa AF: 0.0162 Hom.: 80

Bravo AF: 0.0384

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000519 AC: 2

ESP6500AA AF: 0.124 AC: 328

ESP6500EA AF: 0.000218 AC: 1

ExAC AF: 0.00918 AC: 1044

Asia WGS AF: 0.00635 AC: 22 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	7.2
DANN	Benign	0.77
Eigen	Benign	-0.89
Eigen_PC	Benign	-0.98
FATHMM_MKL	Benign	0.027	N
LIST_S2	Benign	0.31	T
MetaRNN	Benign	0.0019	T
MetaSVM	Benign	-1.1	T
MutationTaster	Benign	1.0	P;P;P;P;P
PROVEAN	Benign	-0.79	N
REVEL	Benign	0.035
Sift	Pathogenic	0.0	D
Polyphen		0.057	B
Vest4		0.11
MVP		0.58
ClinPred		0.031	T
GERP RS		0.36

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: rs34050429; hg19: chr12-52380898;