rs6439886

Variant names:

• chr3-139963653-A-G
• rs6439886
• NM_022131.3:c.109+28170A>G

Variant summary

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

The NM_022131.3(CLSTN2):​c.109+28170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.139 in 152,192 control chromosomes in the GnomAD database, including 1,604 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 0.14 (1604 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.348
• Publications: 19 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.175 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.109+28170A>G		intron_variant	Intron 1 of 16	ENST00000458420.7	NP_071414.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7	c.109+28170A>G		intron_variant	Intron 1 of 16	1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.297+28170A>G		intron_variant	Intron 1 of 10	2

Frequencies

GnomAD3 genomes AF: 0.139 AC: 21074 AN: 152074 Hom.: 1602 Cov.: 32

Gnomad AFR AF: 0.178

Gnomad AMI AF: 0.0976

Gnomad AMR AF: 0.0866

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0849

Gnomad SAS AF: 0.0935

Gnomad FIN AF: 0.148

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.139 AC: 21090 AN: 152192 Hom.: 1604 Cov.: 32 AF XY: 0.136 AC XY: 10125 AN XY: 74402

African (AFR) AF: 0.178 AC: 7396 AN: 41520

American (AMR) AF: 0.0866 AC: 1324 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.136 AC: 472 AN: 3470

East Asian (EAS) AF: 0.0851 AC: 440 AN: 5170

South Asian (SAS) AF: 0.0929 AC: 448 AN: 4820

European-Finnish (FIN) AF: 0.148 AC: 1568 AN: 10594

Middle Eastern (MID) AF: 0.0782 AC: 23 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9085 AN: 68006

Other (OTH) AF: 0.116 AC: 245 AN: 2114

Alfa AF: 0.132 Hom.: 5463

Bravo AF: 0.136

Asia WGS AF: 0.0820 AC: 287 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.5
DANN	Benign	0.73
PhyloP100		0.35
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: rs6439886; hg19: chr3-139682495;