NM_145259.3:c.943+241_943+242dupAA

Variant names:

• chr2-157544202-A-ATT
• rs765521635
• NM_145259.3:c.943+241_943+242dupAA

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_145259.3(ACVR1C):​c.943+241_943+242dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00103 in 116,916 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0010 (2 hom., cov: 25)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.23

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 -4 ACMG points.

• BS2: High AC in GnomAd4 at 120 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ACVR1C	NM_145259.3	c.943+241_943+242dupAA		intron_variant	Intron 5 of 8	ENST00000243349.13	NP_660302.2
ACVR1C	NM_001111031.2	c.793+241_793+242dupAA		intron_variant	Intron 5 of 8		NP_001104501.1
ACVR1C	NM_001111032.2	c.703+241_703+242dupAA		intron_variant	Intron 4 of 7		NP_001104502.1
ACVR1C	NM_001111033.2	c.472+241_472+242dupAA		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.943+242_943+243insAA		intron_variant	Intron 5 of 8	1	NM_145259.3	ENSP00000243349.7
ACVR1C	ENST00000409680.7	c.793+242_793+243insAA		intron_variant	Intron 5 of 8	1		ENSP00000387168.3
ACVR1C	ENST00000335450.7	c.703+242_703+243insAA		intron_variant	Intron 4 of 7	1		ENSP00000335178.7
ACVR1C	ENST00000348328.9	c.472+242_472+243insAA		intron_variant	Intron 3 of 6	1		ENSP00000335139.6

Frequencies

GnomAD3 genomes AF: 0.00103 AC: 120 AN: 116946 Hom.: 2 Cov.: 25

Gnomad AFR AF: 0.00336

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000265

Gnomad ASJ AF: 0.00103

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000161

Gnomad OTH AF: 0.00131

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

GnomAD4 genome AF: 0.00103 AC: 120 AN: 116916 Hom.: 2 Cov.: 25 AF XY: 0.000983 AC XY: 55 AN XY: 55954

Gnomad4 AFR AF: 0.00336

Gnomad4 AMR AF: 0.000265

Gnomad4 ASJ AF: 0.00103

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000161

Gnomad4 OTH AF: 0.00131

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs765521635; hg19: chr2-158400714;