3-140066032-A-G

Variant names:

• chr3-140066032-A-G
• rs2350488
• NM_022131.3:c.110-109919A>G

Variant summary

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

The NM_022131.3(CLSTN2):​c.110-109919A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,032 control chromosomes in the GnomAD database, including 25,542 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 0.56 (25542 hom., cov: 33)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.263
• Publications: 7 publications found

Genes affected

CLSTN2 (HGNC:17448): (calsyntenin 2) Predicted to enable calcium ion binding activity. Predicted to be involved in positive regulation of synapse assembly and positive regulation of synaptic transmission. Predicted to be located in postsynaptic density. Predicted to be active in cell surface; glutamatergic synapse; and postsynaptic membrane. Predicted to be integral component of postsynaptic density membrane. [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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.746 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.110-109919A>G		intron_variant	Intron 1 of 16	ENST00000458420.7	NP_071414.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7	c.110-109919A>G		intron_variant	Intron 1 of 16	1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.298-109919A>G		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85622 AN: 151914 Hom.: 25492 Cov.: 33

Gnomad AFR AF: 0.753

Gnomad AMI AF: 0.507

Gnomad AMR AF: 0.633

Gnomad ASJ AF: 0.313

Gnomad EAS AF: 0.619

Gnomad SAS AF: 0.446

Gnomad FIN AF: 0.478

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.466

Gnomad OTH AF: 0.538

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

GnomAD4 genome AF: 0.564 AC: 85734 AN: 152032 Hom.: 25542 Cov.: 33 AF XY: 0.565 AC XY: 41973 AN XY: 74316

African (AFR) AF: 0.753 AC: 31222 AN: 41462

American (AMR) AF: 0.633 AC: 9675 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.313 AC: 1084 AN: 3460

East Asian (EAS) AF: 0.620 AC: 3204 AN: 5170

South Asian (SAS) AF: 0.446 AC: 2145 AN: 4812

European-Finnish (FIN) AF: 0.478 AC: 5049 AN: 10572

Middle Eastern (MID) AF: 0.414 AC: 121 AN: 292

European-Non Finnish (NFE) AF: 0.466 AC: 31638 AN: 67962

Other (OTH) AF: 0.537 AC: 1134 AN: 2112

Alfa AF: 0.509 Hom.: 57230

Bravo AF: 0.586

Asia WGS AF: 0.503 AC: 1752 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.2
DANN	Benign	0.35
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

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: rs2350488; hg19: chr3-139784874;