rs6806737

Positions:

• chr3-139969573-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.109+34090G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 152,082 control chromosomes in the GnomAD database, including 1,497 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 0.13 (1497 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.65

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.162 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.109+34090G>A		intron_variant		ENST00000458420.7	NP_071414.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7	c.109+34090G>A		intron_variant		1	NM_022131.3	ENSP00000402460	P1
CLSTN2	ENST00000511524.1	n.297+34090G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.135 AC: 20492 AN: 151964 Hom.: 1495 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0850

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0858

Gnomad SAS AF: 0.0886

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0701

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.135 AC: 20504 AN: 152082 Hom.: 1497 Cov.: 32 AF XY: 0.132 AC XY: 9839 AN XY: 74340

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.0850

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0860

Gnomad4 SAS AF: 0.0880

Gnomad4 FIN AF: 0.148

Gnomad4 NFE AF: 0.134

Gnomad4 OTH AF: 0.115

Alfa AF: 0.128 Hom.: 1755

Bravo AF: 0.131

Asia WGS AF: 0.0790 AC: 277 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.037
DANN	Benign	0.37

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: rs6806737; hg19: chr3-139688415;