NM_004302.5:c.*1390C>A

Variant names:

• chr12-51995500-C-A
• rs2714
• NM_004302.5:c.*1390C>A

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 6 publications found

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]

ACVR1B Gene-Disease associations (from GenCC):

• malignant pancreatic neoplasm

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.37).
• BS2: High Homozygotes in GnomAd4 at 5 Unknown gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004302.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1B	NM_004302.5	MANE Select	c.*1390C>A		3_prime_UTR	Exon 9 of 9	NP_004293.1	P36896-1
	ACVR1B	NM_020328.4		c.*1390C>A		3_prime_UTR	Exon 10 of 10	NP_064733.3
	ACVR1B	NM_001412774.1		c.*1390C>A		3_prime_UTR	Exon 10 of 10	NP_001399703.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1B	ENST00000257963.9	TSL:1 MANE Select	c.*1390C>A		3_prime_UTR	Exon 9 of 9	ENSP00000257963.4	P36896-1
	ACVR1B	ENST00000900350.1		c.*1390C>A		3_prime_UTR	Exon 10 of 10	ENSP00000570409.1
	ACVR1B	ENST00000900349.1		c.*1390C>A		3_prime_UTR	Exon 9 of 9	ENSP00000570408.1

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.00 AC: 0 AN: 2

European-Finnish (FIN) AF: 0.00469 AC: 2 AN: 426

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 4

Other (OTH) AF: 0.00 AC: 0 AN: 4

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.00135 AC: 56 AN: 41488

American (AMR) AF: 0.00609 AC: 93 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000866 AC: 3 AN: 3466

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4816

European-Finnish (FIN) AF: 0.00236 AC: 25 AN: 10580

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00700 AC: 476 AN: 67982

Other (OTH) AF: 0.00665 AC: 14 AN: 2106

Alfa AF: 0.00358 Hom.: 1

Bravo AF: 0.00539

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	18
DANN	Benign	0.81
PhyloP100		1.8
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs2714; hg19: chr12-52389284;