rs4683505

Variant names:

• chr3-140528335-C-T
• rs4683505
• NM_022131.3:c.1345-3989C>T

Variant summary

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

The NM_022131.3(CLSTN2):​c.1345-3989C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 152,208 control chromosomes in the GnomAD database, including 738 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 0.070 (738 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.279
• Publications: 5 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]

CLSTN2-AS1 (HGNC:49095): (CLSTN2 antisense RNA 1)

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 (EAS) allele frequency at 95% confidence interval = 0.286 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.1345-3989C>T		intron_variant	Intron 8 of 16	ENST00000458420.7	NP_071414.2
CLSTN2	XM_017007022.3	c.1270-3989C>T		intron_variant	Intron 8 of 16		XP_016862511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7	c.1345-3989C>T		intron_variant	Intron 8 of 16	1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.1533-3989C>T		intron_variant	Intron 8 of 10	2
CLSTN2-AS1	ENST00000816745.1	n.444-22170G>A		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.0702 AC: 10682 AN: 152090 Hom.: 734 Cov.: 32

Gnomad AFR AF: 0.0417

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.0274

Gnomad EAS AF: 0.298

Gnomad SAS AF: 0.0973

Gnomad FIN AF: 0.0821

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0428

Gnomad OTH AF: 0.0612

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

GnomAD4 genome AF: 0.0703 AC: 10694 AN: 152208 Hom.: 738 Cov.: 32 AF XY: 0.0763 AC XY: 5681 AN XY: 74424

African (AFR) AF: 0.0416 AC: 1730 AN: 41540

American (AMR) AF: 0.193 AC: 2951 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0274 AC: 95 AN: 3468

East Asian (EAS) AF: 0.298 AC: 1542 AN: 5168

South Asian (SAS) AF: 0.0970 AC: 466 AN: 4806

European-Finnish (FIN) AF: 0.0821 AC: 872 AN: 10618

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0428 AC: 2910 AN: 68004

Other (OTH) AF: 0.0597 AC: 126 AN: 2112

Alfa AF: 0.0560 Hom.: 940

Bravo AF: 0.0793

Asia WGS AF: 0.208 AC: 724 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	3.7
DANN	Benign	0.29
PhyloP100		-0.28
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: rs4683505; hg19: chr3-140247177;