rs17411949

Variant names:

• chr3-140380851-C-T
• rs17411949
• NM_022131.3:c.233-22778C>T

Variant summary

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

The NM_022131.3(CLSTN2):​c.233-22778C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.045 in 152,222 control chromosomes in the GnomAD database, including 182 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 0.045 (182 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.746

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=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.233-22778C>T		intron_variant	Intron 2 of 16	ENST00000458420.7	NP_071414.2
CLSTN2	XM_017007022.3	c.158-22778C>T		intron_variant	Intron 2 of 16		XP_016862511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7	c.233-22778C>T		intron_variant	Intron 2 of 16	1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.421-22778C>T		intron_variant	Intron 2 of 10	2

Frequencies

GnomAD3 genomes AF: 0.0450 AC: 6840 AN: 152106 Hom.: 177 Cov.: 32

Gnomad AFR AF: 0.0372

Gnomad AMI AF: 0.0439

Gnomad AMR AF: 0.0448

Gnomad ASJ AF: 0.0352

Gnomad EAS AF: 0.0599

Gnomad SAS AF: 0.0674

Gnomad FIN AF: 0.0139

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0520

Gnomad OTH AF: 0.0550

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

GnomAD4 genome AF: 0.0450 AC: 6852 AN: 152222 Hom.: 182 Cov.: 32 AF XY: 0.0439 AC XY: 3265 AN XY: 74410

Gnomad4 AFR AF: 0.0371

Gnomad4 AMR AF: 0.0448

Gnomad4 ASJ AF: 0.0352

Gnomad4 EAS AF: 0.0599

Gnomad4 SAS AF: 0.0673

Gnomad4 FIN AF: 0.0139

Gnomad4 NFE AF: 0.0520

Gnomad4 OTH AF: 0.0596

Alfa AF: 0.0517 Hom.: 306

Bravo AF: 0.0468

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.1
DANN	Benign	0.41

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: rs17411949; hg19: chr3-140099693;