2-157544202-ATTTTTTTTTTT-ATTTTTTTT

Variant names:

• chr2-157544202-ATTT-A
• rs765521635
• NM_145259.3:c.943+240_943+242delAAA

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_145259.3(ACVR1C):​c.943+240_943+242delAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000128 in 116,928 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.00013 (0 hom., cov: 25)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.851
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 15 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.943+240_943+242delAAA		intron	N/A	NP_660302.2	Q8NER5-1
	ACVR1C	NM_001111031.2		c.793+240_793+242delAAA		intron	N/A	NP_001104501.1	Q8NER5-4
	ACVR1C	NM_001111032.2		c.703+240_703+242delAAA		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.943+240_943+242delAAA		intron	N/A	ENSP00000243349.7	Q8NER5-1
	ACVR1C	ENST00000409680.7	TSL:1	c.793+240_793+242delAAA		intron	N/A	ENSP00000387168.3	Q8NER5-4
	ACVR1C	ENST00000335450.7	TSL:1	c.703+240_703+242delAAA		intron	N/A	ENSP00000335178.7	Q8NER5-3

Frequencies

GnomAD3 genomes AF: 0.000111 AC: 13 AN: 116958 Hom.: 0 Cov.: 25

Gnomad AFR AF: 0.000425

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.000128 AC: 15 AN: 116928 Hom.: 0 Cov.: 25 AF XY: 0.000179 AC XY: 10 AN XY: 55956

African (AFR) AF: 0.000489 AC: 15 AN: 30652

American (AMR) AF: 0.00 AC: 0 AN: 11340

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2904

East Asian (EAS) AF: 0.00 AC: 0 AN: 4148

South Asian (SAS) AF: 0.00 AC: 0 AN: 3758

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 200

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 56026

Other (OTH) AF: 0.00 AC: 0 AN: 1528

Alfa AF: 0.00 Hom.: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.85

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: rs765521635; hg19: chr2-158400714;