chr2-157538753-A-T

Variant names:

• chr2-157538753-A-T
• NM_145259.3:c.1226-50T>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_145259.3(ACVR1C):​c.1226-50T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000319 in 1,254,128 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.0000032 (0 hom.)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.310

Genes affected

ACVR1C (HGNC:18123): (activin A receptor type 1C) ACVR1C is a type I receptor for the TGFB (see MIM 190180) family of signaling molecules. Upon ligand binding, type I receptors phosphorylate cytoplasmic SMAD transcription factors, which then translocate to the nucleus and interact directly with DNA or in complex with other transcription factors (Bondestam et al., 2001 [PubMed 12063393]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.1226-50T>A		intron_variant	Intron 7 of 8	ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.1076-50T>A		intron_variant	Intron 7 of 8		NP_001104501.1
ACVR1C	NM_001111032.2	c.986-50T>A		intron_variant	Intron 6 of 7		NP_001104502.1
ACVR1C	NM_001111033.2	c.755-50T>A		intron_variant	Intron 5 of 6		NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.1226-50T>A		intron_variant	Intron 7 of 8	1	NM_145259.3	ENSP00000243349.7
ACVR1C	ENST00000409680.7	c.1076-50T>A		intron_variant	Intron 7 of 8	1		ENSP00000387168.3
ACVR1C	ENST00000335450.7	c.986-50T>A		intron_variant	Intron 6 of 7	1		ENSP00000335178.7
ACVR1C	ENST00000348328.9	c.755-50T>A		intron_variant	Intron 5 of 6	1		ENSP00000335139.6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000319 AC: 4 AN: 1254128 Hom.: 0 Cov.: 23 AF XY: 0.00000489 AC XY: 3 AN XY: 613934

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000400

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.4
DANN	Benign	0.68

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-158395265;