rs1834497

Positions:

• chr3-140008425-A-G

Variant summary

Our verdict is Benign. Variant got -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

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.109+72942A>G		intron_variant		ENST00000458420.7	NP_071414.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7	c.109+72942A>G		intron_variant		1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.297+72942A>G		intron_variant		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

Gnomad4 AFR AF: 0.724

Gnomad4 AMR AF: 0.623

Gnomad4 ASJ AF: 0.451

Gnomad4 EAS AF: 0.792

Gnomad4 SAS AF: 0.516

Gnomad4 FIN AF: 0.489

Gnomad4 NFE AF: 0.471

Gnomad4 OTH AF: 0.555

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs1834497; hg19: chr3-139727267;