2-157544202-ATT-A

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_145259.3(ACVR1C):​c.943+241_943+242delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0134 in 116,868 control chromosomes in the GnomAD database, including 22 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.013 (22 hom., cov: 25)
• Consequence: ACVR1C NM_145259.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.842
• 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: Benign. The variant received -10 ACMG points.

• BP6: Variant 2-157544202-ATT-A is Benign according to our data. Variant chr2-157544202-ATT-A is described in ClinVar as Benign. ClinVar VariationId is 1235792.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0134 (1561/116868) while in subpopulation AFR AF = 0.0476 (1456/30606). AF 95% confidence interval is 0.0455. There are 22 homozygotes in GnomAd4. There are 726 alleles in the male GnomAd4 subpopulation. Median coverage is 25. This position passed quality control check.
• BS2: High AC in GnomAd4 at 1561 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+241_943+242delAA		intron	N/A	NP_660302.2	Q8NER5-1
	ACVR1C	NM_001111031.2		c.793+241_793+242delAA		intron	N/A	NP_001104501.1	Q8NER5-4
	ACVR1C	NM_001111032.2		c.703+241_703+242delAA		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+241_943+242delAA		intron	N/A	ENSP00000243349.7	Q8NER5-1
	ACVR1C	ENST00000409680.7	TSL:1	c.793+241_793+242delAA		intron	N/A	ENSP00000387168.3	Q8NER5-4
	ACVR1C	ENST00000335450.7	TSL:1	c.703+241_703+242delAA		intron	N/A	ENSP00000335178.7	Q8NER5-3

Frequencies

GnomAD3 genomes AF: 0.0133 AC: 1558 AN: 116898 Hom.: 21 Cov.: 25

Gnomad AFR AF: 0.0475

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00565

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000264

Gnomad FIN AF: 0.000537

Gnomad MID AF: 0.00901

Gnomad NFE AF: 0.000250

Gnomad OTH AF: 0.0138

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

GnomAD4 genome AF: 0.0134 AC: 1561 AN: 116868 Hom.: 22 Cov.: 25 AF XY: 0.0130 AC XY: 726 AN XY: 55922

African (AFR) AF: 0.0476 AC: 1456 AN: 30606

American (AMR) AF: 0.00565 AC: 64 AN: 11336

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

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

South Asian (SAS) AF: 0.000266 AC: 1 AN: 3758

European-Finnish (FIN) AF: 0.000537 AC: 3 AN: 5582

Middle Eastern (MID) AF: 0.0100 AC: 2 AN: 200

European-Non Finnish (NFE) AF: 0.000250 AC: 14 AN: 56022

Other (OTH) AF: 0.0138 AC: 21 AN: 1526

Alfa AF: 0.00 Hom.: 2

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.84
Mutation Taster		=100/0	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: rs765521635; hg19: chr2-158400714;