rs6439924

Variant names:

• chr3-140450815-A-C
• rs6439924
• NM_022131.3:c.973+2111A>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.973+2111A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,114 control chromosomes in the GnomAD database, including 3,945 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 0.21 (3945 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.19
• Publications: 12 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]

ENSG00000249290 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.973+2111A>C		intron_variant	Intron 6 of 16	ENST00000458420.7	NP_071414.2
CLSTN2	XM_017007022.3	c.898+2111A>C		intron_variant	Intron 6 of 16		XP_016862511.1
LOC124900599	XR_924548.3	n.86-772T>G		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7	c.973+2111A>C		intron_variant	Intron 6 of 16	1	NM_022131.3	ENSP00000402460.2
ENSG00000249290	ENST00000502712.5	n.351-772T>G		intron_variant	Intron 3 of 4	5
ENSG00000249290	ENST00000509191.5	n.430-772T>G		intron_variant	Intron 4 of 5	3
CLSTN2	ENST00000511524.1	n.1161+2111A>C		intron_variant	Intron 6 of 10	2

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31813 AN: 151996 Hom.: 3943 Cov.: 32

Gnomad AFR AF: 0.341

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.153

Gnomad ASJ AF: 0.206

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.0734

Gnomad FIN AF: 0.130

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.203

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

GnomAD4 genome AF: 0.209 AC: 31843 AN: 152114 Hom.: 3945 Cov.: 32 AF XY: 0.202 AC XY: 15005 AN XY: 74356

African (AFR) AF: 0.341 AC: 14149 AN: 41456

American (AMR) AF: 0.153 AC: 2341 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.206 AC: 715 AN: 3470

East Asian (EAS) AF: 0.116 AC: 603 AN: 5176

South Asian (SAS) AF: 0.0726 AC: 350 AN: 4818

European-Finnish (FIN) AF: 0.130 AC: 1378 AN: 10596

Middle Eastern (MID) AF: 0.288 AC: 84 AN: 292

European-Non Finnish (NFE) AF: 0.171 AC: 11656 AN: 67986

Other (OTH) AF: 0.202 AC: 427 AN: 2112

Alfa AF: 0.186 Hom.: 8880

Bravo AF: 0.219

Asia WGS AF: 0.121 AC: 420 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.73
PhyloP100		1.2
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: rs6439924; hg19: chr3-140169657;