rs16849640

Positions:

• chr3-140000523-A-T

Variant summary

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

The NM_022131.3(CLSTN2):​c.109+65040A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0773 in 152,228 control chromosomes in the GnomAD database, including 492 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 0.077 (492 hom., cov: 32)
• Consequence: CLSTN2 NM_022131.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0910

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=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLSTN2	NM_022131.3	c.109+65040A>T		intron_variant		ENST00000458420.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLSTN2	ENST00000458420.7	c.109+65040A>T		intron_variant		1	NM_022131.3	P1
CLSTN2	ENST00000511524.1	n.297+65040A>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0774 AC: 11766 AN: 152110 Hom.: 493 Cov.: 32

Gnomad AFR AF: 0.0824

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.0668

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.141

Gnomad SAS AF: 0.0234

Gnomad FIN AF: 0.0637

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0741

Gnomad OTH AF: 0.0686

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

GnomAD4 genome AF: 0.0773 AC: 11764 AN: 152228 Hom.: 492 Cov.: 32 AF XY: 0.0753 AC XY: 5603 AN XY: 74416

Gnomad4 AFR AF: 0.0823

Gnomad4 AMR AF: 0.0667

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.141

Gnomad4 SAS AF: 0.0234

Gnomad4 FIN AF: 0.0637

Gnomad4 NFE AF: 0.0741

Gnomad4 OTH AF: 0.0678

Alfa AF: 0.0750 Hom.: 68

Bravo AF: 0.0790

Asia WGS AF: 0.0610 AC: 212 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.0
DANN	Benign	0.48

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: rs16849640; hg19: chr3-139719365;