rs9862730

chr3-140504952-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_022131.3(CLSTN2):c.1345-27372G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,112 control chromosomes in the GnomAD database, including 2,393 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 0.15 (2393 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.299

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.302 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLSTN2	NM_022131.3	c.1345-27372G>A		intron_variant		ENST00000458420.7
CLSTN2	XM_017007022.3	c.1270-27372G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLSTN2	ENST00000458420.7	c.1345-27372G>A		intron_variant		1	NM_022131.3	P1
CLSTN2	ENST00000511524.1	n.1533-27372G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22462 AN: 151994 Hom.: 2393 Cov.: 32

Gnomad AFR AF: 0.307

Gnomad AMI AF: 0.0187

Gnomad AMR AF: 0.121

Gnomad ASJ AF: 0.0559

Gnomad EAS AF: 0.0519

Gnomad SAS AF: 0.0324

Gnomad FIN AF: 0.0510

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0953

Gnomad OTH AF: 0.128

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

GnomAD4 genome AF: 0.148 AC: 22491 AN: 152112 Hom.: 2393 Cov.: 32 AF XY: 0.142 AC XY: 10569 AN XY: 74354

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.121

Gnomad4 ASJ AF: 0.0559

Gnomad4 EAS AF: 0.0520

Gnomad4 SAS AF: 0.0324

Gnomad4 FIN AF: 0.0510

Gnomad4 NFE AF: 0.0953

Gnomad4 OTH AF: 0.126

Alfa AF: 0.106 Hom.: 1165

Bravo AF: 0.159

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	6.7
Dann	Benign	0.82

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: rs9862730; hg19: chr3-140223794;