3-140446678-G-C

Variant names:

• chr3-140446678-G-C
• rs13086670
• NM_022131.3:c.788-1841G>C

Variant summary

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

The NM_022131.3(CLSTN2):​c.788-1841G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 151,912 control chromosomes in the GnomAD database, including 12,935 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 0.39 (12935 hom., cov: 31)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.455
• Publications: 1 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.497 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.788-1841G>C		intron_variant	Intron 5 of 16	ENST00000458420.7	NP_071414.2
CLSTN2	XM_017007022.3	c.713-1841G>C		intron_variant	Intron 5 of 16		XP_016862511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7	c.788-1841G>C		intron_variant	Intron 5 of 16	1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.976-1841G>C		intron_variant	Intron 5 of 10	2

Frequencies

GnomAD3 genomes AF: 0.388 AC: 58866 AN: 151794 Hom.: 12930 Cov.: 31

Gnomad AFR AF: 0.210

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.345

Gnomad ASJ AF: 0.476

Gnomad EAS AF: 0.0750

Gnomad SAS AF: 0.448

Gnomad FIN AF: 0.489

Gnomad MID AF: 0.490

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.407

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

GnomAD4 genome AF: 0.388 AC: 58879 AN: 151912 Hom.: 12935 Cov.: 31 AF XY: 0.387 AC XY: 28709 AN XY: 74240

African (AFR) AF: 0.210 AC: 8707 AN: 41424

American (AMR) AF: 0.344 AC: 5255 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.476 AC: 1652 AN: 3472

East Asian (EAS) AF: 0.0745 AC: 386 AN: 5178

South Asian (SAS) AF: 0.449 AC: 2152 AN: 4788

European-Finnish (FIN) AF: 0.489 AC: 5157 AN: 10542

Middle Eastern (MID) AF: 0.507 AC: 148 AN: 292

European-Non Finnish (NFE) AF: 0.502 AC: 34090 AN: 67936

Other (OTH) AF: 0.406 AC: 855 AN: 2108

Alfa AF: 0.448 Hom.: 2054

Bravo AF: 0.368

Asia WGS AF: 0.221 AC: 768 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	3.2
DANN	Benign	0.75
PhyloP100		0.46
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: rs13086670; hg19: chr3-140165520;