rs6746788

Variant names:

• chr2-157544593-T-C
• rs6746788
• NM_145259.3:c.795A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-157544593-T-C
• chr2-157544593-T-G

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_145259.3(ACVR1C):​c.795A>G​(p.Gln265Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00273 in 1,611,678 control chromosomes in the GnomAD database, including 107 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.014 (56 hom., cov: 32)
  • Exomes 𝑓: 0.0015 (51 hom.)
• Consequence: ACVR1C NM_145259.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.222
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 2-157544593-T-C is Benign according to our data. Variant chr2-157544593-T-C is described in ClinVar as Benign. ClinVar VariationId is 783343.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.222 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0141 (2142/152278) while in subpopulation AFR AF = 0.0484 (2010/41520). AF 95% confidence interval is 0.0466. There are 56 homozygotes in GnomAd4. There are 997 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2142 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_145259.3. 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
	ACVR1C	NM_145259.3	MANE Select	c.795A>G	p.Gln265Gln	synonymous	Exon 5 of 9	NP_660302.2	Q8NER5-1
	ACVR1C	NM_001111031.2		c.645A>G	p.Gln215Gln	synonymous	Exon 5 of 9	NP_001104501.1	Q8NER5-4
	ACVR1C	NM_001111032.2		c.555A>G	p.Gln185Gln	synonymous	Exon 4 of 8	NP_001104502.1	Q8NER5-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACVR1C	ENST00000243349.13	TSL:1 MANE Select	c.795A>G	p.Gln265Gln	synonymous	Exon 5 of 9	ENSP00000243349.7	Q8NER5-1
	ACVR1C	ENST00000409680.7	TSL:1	c.645A>G	p.Gln215Gln	synonymous	Exon 5 of 9	ENSP00000387168.3	Q8NER5-4
	ACVR1C	ENST00000335450.7	TSL:1	c.555A>G	p.Gln185Gln	synonymous	Exon 4 of 8	ENSP00000335178.7	Q8NER5-3

Frequencies

GnomAD3 genomes AF: 0.0141 AC: 2143 AN: 152160 Hom.: 57 Cov.: 32

Gnomad AFR AF: 0.0486

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00615

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.00908

GnomAD2 exomes AF: 0.00433 AC: 1077 AN: 248730 AF XY: 0.00313

Gnomad AFR exome AF: 0.0518

Gnomad AMR exome AF: 0.00509

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000310

Gnomad OTH exome AF: 0.00460

GnomAD4 exome AF: 0.00154 AC: 2253 AN: 1459400 Hom.: 51 Cov.: 32 AF XY: 0.00137 AC XY: 994 AN XY: 725956

African (AFR) AF: 0.0458 AC: 1529 AN: 33358

American (AMR) AF: 0.00537 AC: 238 AN: 44298

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26046

East Asian (EAS) AF: 0.00 AC: 0 AN: 39662

South Asian (SAS) AF: 0.0000584 AC: 5 AN: 85546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53376

Middle Eastern (MID) AF: 0.00295 AC: 17 AN: 5754

European-Non Finnish (NFE) AF: 0.000244 AC: 271 AN: 1111058

Other (OTH) AF: 0.00320 AC: 193 AN: 60302

GnomAD4 genome AF: 0.0141 AC: 2142 AN: 152278 Hom.: 56 Cov.: 32 AF XY: 0.0134 AC XY: 997 AN XY: 74472

African (AFR) AF: 0.0484 AC: 2010 AN: 41520

American (AMR) AF: 0.00614 AC: 94 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000235 AC: 16 AN: 68030

Other (OTH) AF: 0.00899 AC: 19 AN: 2114

Alfa AF: 0.00797 Hom.: 8

Bravo AF: 0.0167

Asia WGS AF: 0.00115 AC: 4 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	ACVR1C-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	4.1
DANN	Benign	0.57
PhyloP100		0.22
Mutation Taster		=99/1	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: rs6746788; hg19: chr2-158401105;