rs2159236

Variant names:

• chr7-150320125-A-G
• rs2159236
• NM_001164458.2:c.-52+3344T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000683684.1(ACTR3C):​c.-52+3344T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,110 control chromosomes in the GnomAD database, including 4,555 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.23 (4555 hom., cov: 33)
• Consequence: ACTR3C ENST00000683684.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.328
• Publications: 10 publications found

Genes affected

ACTR3C (HGNC:37282): (actin related protein 3C) Predicted to enable ATP binding activity. Predicted to contribute to actin filament binding activity. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

LRRC61 (HGNC:21704): (leucine rich repeat containing 61) Predicted to be active in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.403 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000683684.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR3C	NM_001164458.2	MANE Select	c.-52+3344T>C		intron	N/A	NP_001157930.1
	LRRC61	NM_001363434.1		c.-314-5716A>G		intron	N/A	NP_001350363.1
	ACTR3C	NM_001351028.2		c.-593+3344T>C		intron	N/A	NP_001337957.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ACTR3C	ENST00000683684.1	MANE Select	c.-52+3344T>C		intron	N/A	ENSP00000507618.1
	ACTR3C	ENST00000478393.5	TSL:1	c.105+3344T>C		intron	N/A	ENSP00000417426.1
	ACTR3C	ENST00000477871.1	TSL:3	c.246+3344T>C		intron	N/A	ENSP00000418635.1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35588 AN: 151992 Hom.: 4563 Cov.: 33

Gnomad AFR AF: 0.153

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.188

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.418

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.282

Gnomad NFE AF: 0.258

Gnomad OTH AF: 0.221

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

GnomAD4 genome AF: 0.234 AC: 35589 AN: 152110 Hom.: 4555 Cov.: 33 AF XY: 0.239 AC XY: 17752 AN XY: 74370

African (AFR) AF: 0.153 AC: 6362 AN: 41472

American (AMR) AF: 0.188 AC: 2871 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1136 AN: 3466

East Asian (EAS) AF: 0.417 AC: 2162 AN: 5180

South Asian (SAS) AF: 0.276 AC: 1329 AN: 4822

European-Finnish (FIN) AF: 0.309 AC: 3273 AN: 10586

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.258 AC: 17566 AN: 67992

Other (OTH) AF: 0.218 AC: 460 AN: 2108

Alfa AF: 0.252 Hom.: 1454

Bravo AF: 0.221

Asia WGS AF: 0.326 AC: 1134 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.6
DANN	Benign	0.72
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs2159236; hg19: chr7-150017214;