NM_145259.3:c.1356+6G>T

Variant names:

• chr2-157538567-C-A
• rs7576514
• NM_145259.3:c.1356+6G>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_145259.3(ACVR1C):​c.1356+6G>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000716 in 1,395,996 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: ACVR1C NM_145259.3 splice_region, intron
• Scores: Splicing: ADA: 0.0007619
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0780

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.26).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.1356+6G>T		splice_region_variant, intron_variant	Intron 8 of 8	ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.1206+6G>T		splice_region_variant, intron_variant	Intron 8 of 8		NP_001104501.1
ACVR1C	NM_001111032.2	c.1116+6G>T		splice_region_variant, intron_variant	Intron 7 of 7		NP_001104502.1
ACVR1C	NM_001111033.2	c.885+6G>T		splice_region_variant, intron_variant	Intron 6 of 6		NP_001104503.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ACVR1C	ENST00000243349.13	c.1356+6G>T		splice_region_variant, intron_variant	Intron 8 of 8	1	NM_145259.3	ENSP00000243349.7
ACVR1C	ENST00000409680.7	c.1206+6G>T		splice_region_variant, intron_variant	Intron 8 of 8	1		ENSP00000387168.3
ACVR1C	ENST00000335450.7	c.1116+6G>T		splice_region_variant, intron_variant	Intron 7 of 7	1		ENSP00000335178.7
ACVR1C	ENST00000348328.9	c.885+6G>T		splice_region_variant, intron_variant	Intron 6 of 6	1		ENSP00000335139.6

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD3 exomes AF: 0.00000476 AC: 1 AN: 210122 Hom.: 0 AF XY: 0.00000875 AC XY: 1 AN XY: 114310

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000986

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.16e-7 AC: 1 AN: 1395996 Hom.: 0 Cov.: 38 AF XY: 0.00000144 AC XY: 1 AN XY: 692492

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: 9.22e-7

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	-0.26
CADD	Benign	12
DANN	Benign	0.91

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00076
dbscSNV1_RF	Benign	0.066
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: rs7576514; hg19: chr2-158395079;