2-157538567-C-G

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BA1

The NM_145259.3(ACVR1C):​c.1356+6G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.875 in 1,547,518 control chromosomes in the GnomAD database, including 593,757 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.86 (56088 hom., cov: 31)
  • Exomes 𝑓: 0.88 (537669 hom.)
• Consequence: ACVR1C NM_145259.3 splice_region, intron
• Scores: Splicing: ADA: 0.005482
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0780
• Publications: 13 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BP6: Variant 2-157538567-C-G is Benign according to our data. Variant chr2-157538567-C-G is described in ClinVar as Benign. ClinVar VariationId is 1263226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.903 is higher than 0.05.

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.1356+6G>C		splice_region intron	N/A	NP_660302.2	Q8NER5-1
	ACVR1C	NM_001111031.2		c.1206+6G>C		splice_region intron	N/A	NP_001104501.1	Q8NER5-4
	ACVR1C	NM_001111032.2		c.1116+6G>C		splice_region intron	N/A	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.1356+6G>C		splice_region intron	N/A	ENSP00000243349.7	Q8NER5-1
	ACVR1C	ENST00000409680.7	TSL:1	c.1206+6G>C		splice_region intron	N/A	ENSP00000387168.3	Q8NER5-4
	ACVR1C	ENST00000335450.7	TSL:1	c.1116+6G>C		splice_region intron	N/A	ENSP00000335178.7	Q8NER5-3

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130292 AN: 152046 Hom.: 56062 Cov.: 31

Gnomad AFR AF: 0.792

Gnomad AMI AF: 0.907

Gnomad AMR AF: 0.904

Gnomad ASJ AF: 0.813

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.777

Gnomad FIN AF: 0.900

Gnomad MID AF: 0.880

Gnomad NFE AF: 0.881

Gnomad OTH AF: 0.862

GnomAD2 exomes AF: 0.871 AC: 183037 AN: 210122 AF XY: 0.867

Gnomad AFR exome AF: 0.792

Gnomad AMR exome AF: 0.933

Gnomad ASJ exome AF: 0.828

Gnomad EAS exome AF: 0.917

Gnomad FIN exome AF: 0.902

Gnomad NFE exome AF: 0.880

Gnomad OTH exome AF: 0.871

GnomAD4 exome AF: 0.877 AC: 1223735 AN: 1395354 Hom.: 537669 Cov.: 38 AF XY: 0.874 AC XY: 605271 AN XY: 692150

African (AFR) AF: 0.784 AC: 23726 AN: 30266

American (AMR) AF: 0.929 AC: 31250 AN: 33628

Ashkenazi Jewish (ASJ) AF: 0.822 AC: 19808 AN: 24084

East Asian (EAS) AF: 0.934 AC: 34533 AN: 36962

South Asian (SAS) AF: 0.772 AC: 55366 AN: 71734

European-Finnish (FIN) AF: 0.902 AC: 46763 AN: 51818

Middle Eastern (MID) AF: 0.838 AC: 4629 AN: 5522

European-Non Finnish (NFE) AF: 0.884 AC: 957917 AN: 1084018

Other (OTH) AF: 0.868 AC: 49743 AN: 57322

GnomAD4 genome AF: 0.857 AC: 130365 AN: 152164 Hom.: 56088 Cov.: 31 AF XY: 0.858 AC XY: 63846 AN XY: 74398

African (AFR) AF: 0.791 AC: 32814 AN: 41482

American (AMR) AF: 0.904 AC: 13819 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.813 AC: 2824 AN: 3472

East Asian (EAS) AF: 0.925 AC: 4794 AN: 5182

South Asian (SAS) AF: 0.777 AC: 3745 AN: 4822

European-Finnish (FIN) AF: 0.900 AC: 9523 AN: 10582

Middle Eastern (MID) AF: 0.881 AC: 259 AN: 294

European-Non Finnish (NFE) AF: 0.881 AC: 59934 AN: 68014

Other (OTH) AF: 0.864 AC: 1826 AN: 2114

Alfa AF: 0.868 Hom.: 18566

Bravo AF: 0.858

Asia WGS AF: 0.868 AC: 3018 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	12
DANN	Benign	0.92
PhyloP100		0.078
Mutation Taster		=90/10	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0055
dbscSNV1_RF	Benign	0.19
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: rs7576514; hg19: chr2-158395079;