rs16849640

Variant names:

• chr3-140000523-A-T
• rs16849640
• NM_022131.3:c.109+65040A>T

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+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
• Publications: 2 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=-0.81).
• 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 rank	MANE	Protein	UniProt
CLSTN2	NM_022131.3	c.109+65040A>T		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+65040A>T		intron_variant	Intron 1 of 16	1	NM_022131.3	ENSP00000402460.2
CLSTN2	ENST00000511524.1	n.297+65040A>T		intron_variant	Intron 1 of 10	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

African (AFR) AF: 0.0823 AC: 3418 AN: 41538

American (AMR) AF: 0.0667 AC: 1021 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3472

East Asian (EAS) AF: 0.141 AC: 726 AN: 5166

South Asian (SAS) AF: 0.0234 AC: 113 AN: 4826

European-Finnish (FIN) AF: 0.0637 AC: 675 AN: 10592

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.0741 AC: 5039 AN: 68028

Other (OTH) AF: 0.0678 AC: 143 AN: 2108

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
PhyloP100		0.091
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: rs16849640; hg19: chr3-139719365;