rs1834497

Variant names:

• chr3-140008425-A-G
• rs1834497
• NM_022131.3:c.109+72942A>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.109+72942A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.57 in 152,144 control chromosomes in the GnomAD database, including 25,718 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 0.57 (25718 hom., cov: 34)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0580
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.772 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.109+72942A>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.109+72942A>G		intron_variant	Intron 1 of 16	1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.297+72942A>G		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.570 AC: 86602 AN: 152026 Hom.: 25689 Cov.: 34

Gnomad AFR AF: 0.724

Gnomad AMI AF: 0.501

Gnomad AMR AF: 0.623

Gnomad ASJ AF: 0.451

Gnomad EAS AF: 0.792

Gnomad SAS AF: 0.517

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.557

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

GnomAD4 genome AF: 0.570 AC: 86680 AN: 152144 Hom.: 25718 Cov.: 34 AF XY: 0.572 AC XY: 42528 AN XY: 74366

African (AFR) AF: 0.724 AC: 30051 AN: 41528

American (AMR) AF: 0.623 AC: 9525 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.451 AC: 1563 AN: 3462

East Asian (EAS) AF: 0.792 AC: 4092 AN: 5168

South Asian (SAS) AF: 0.516 AC: 2487 AN: 4824

European-Finnish (FIN) AF: 0.489 AC: 5172 AN: 10574

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32024 AN: 67986

Other (OTH) AF: 0.555 AC: 1170 AN: 2110

Alfa AF: 0.529 Hom.: 3739

Bravo AF: 0.592

Asia WGS AF: 0.652 AC: 2266 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	4.5
DANN	Benign	0.52
PhyloP100		0.058
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: rs1834497; hg19: chr3-139727267;