rs4461222

Variant names:

• chr2-157543002-G-A
• rs4461222
• NM_145259.3:c.944-140C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-157543002-G-A
• chr2-157543002-G-C
• chr2-157543002-G-T

Variant summary

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

The NM_145259.3(ACVR1C):​c.944-140C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0670

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=-0.7).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.944-140C>T		intron_variant	Intron 5 of 8	ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.794-140C>T		intron_variant	Intron 5 of 8		NP_001104501.1
ACVR1C	NM_001111032.2	c.704-140C>T		intron_variant	Intron 4 of 7		NP_001104502.1
ACVR1C	NM_001111033.2	c.473-140C>T		intron_variant	Intron 3 of 6		NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.944-140C>T		intron_variant	Intron 5 of 8	1	NM_145259.3	ENSP00000243349.7
ACVR1C	ENST00000409680.7	c.794-140C>T		intron_variant	Intron 5 of 8	1		ENSP00000387168.3
ACVR1C	ENST00000335450.7	c.704-140C>T		intron_variant	Intron 4 of 7	1		ENSP00000335178.7
ACVR1C	ENST00000348328.9	c.473-140C>T		intron_variant	Intron 3 of 6	1		ENSP00000335139.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 631460 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 327346

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	9.5
DANN	Benign	0.82

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: rs4461222; hg19: chr2-158399514;