rs11708189

chr3-140456518-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.974-3003G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.595 in 152,120 control chromosomes in the GnomAD database, including 27,893 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 0.60 (27893 hom., cov: 33)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLSTN2	NM_022131.3	c.974-3003G>A		intron_variant		ENST00000458420.7
LOC105374132	XR_007096117.1	n.49-1765C>T		intron_variant, non_coding_transcript_variant
CLSTN2	XM_017007022.3	c.899-3003G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLSTN2	ENST00000458420.7	c.974-3003G>A		intron_variant		1	NM_022131.3	P1
	ENST00000503357.1	n.101-1765C>T		intron_variant, non_coding_transcript_variant		3
CLSTN2	ENST00000511524.1	n.1162-3003G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.595 AC: 90515 AN: 152002 Hom.: 27881 Cov.: 33

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.497

Gnomad ASJ AF: 0.683

Gnomad EAS AF: 0.188

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.618

Gnomad MID AF: 0.785

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.608

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

GnomAD4 genome AF: 0.595 AC: 90554 AN: 152120 Hom.: 27893 Cov.: 33 AF XY: 0.587 AC XY: 43680 AN XY: 74378

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.496

Gnomad4 ASJ AF: 0.683

Gnomad4 EAS AF: 0.188

Gnomad4 SAS AF: 0.522

Gnomad4 FIN AF: 0.618

Gnomad4 NFE AF: 0.672

Gnomad4 OTH AF: 0.606

Alfa AF: 0.648 Hom.: 70059

Bravo AF: 0.584

Asia WGS AF: 0.340 AC: 1182 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.8
Dann	Benign	0.21

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: rs11708189; hg19: chr3-140175360;