rs4605505

Variant names:

• chr3-140122044-G-A
• rs4605505
• NM_022131.3:c.110-53907G>A

Your query was ambiguous. Multiple possible variants found:

• chr3-140122044-G-A
• chr3-140122044-G-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.110-53907G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 152,110 control chromosomes in the GnomAD database, including 3,282 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 0.19 (3282 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.24
• Publications: 5 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.362 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.110-53907G>A		intron_variant	Intron 1 of 16	ENST00000458420.7	NP_071414.2
CLSTN2	XM_017007022.3	c.34+29103G>A		intron_variant	Intron 1 of 16		XP_016862511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7	c.110-53907G>A		intron_variant	Intron 1 of 16	1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.298-53907G>A		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.188 AC: 28604 AN: 151992 Hom.: 3267 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.102

Gnomad MID AF: 0.134

Gnomad NFE AF: 0.127

Gnomad OTH AF: 0.177

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

GnomAD4 genome AF: 0.188 AC: 28672 AN: 152110 Hom.: 3282 Cov.: 32 AF XY: 0.190 AC XY: 14124 AN XY: 74356

African (AFR) AF: 0.304 AC: 12584 AN: 41458

American (AMR) AF: 0.149 AC: 2275 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 453 AN: 3468

East Asian (EAS) AF: 0.376 AC: 1948 AN: 5176

South Asian (SAS) AF: 0.240 AC: 1158 AN: 4818

European-Finnish (FIN) AF: 0.102 AC: 1086 AN: 10596

Middle Eastern (MID) AF: 0.137 AC: 40 AN: 292

European-Non Finnish (NFE) AF: 0.127 AC: 8631 AN: 67992

Other (OTH) AF: 0.183 AC: 386 AN: 2112

Alfa AF: 0.143 Hom.: 3047

Bravo AF: 0.195

Asia WGS AF: 0.322 AC: 1118 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.44
DANN	Benign	0.76
PhyloP100		-2.2
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: rs4605505; hg19: chr3-139840886;