Variant chr3-140403621-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_022131.3(CLSTN2):c.233-8T>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0026 in 1,600,578 control chromosomes in the GnomAD database, including 87 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.014 ( 37 hom., cov: 32)

Exomes 𝑓: 0.0014 ( 50 hom. )

Consequence

CLSTN2
NM_022131.3 splice_region, intron

Scores

Splicing: ADA: 0.005154

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.919

Variant links:

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]

CLSTN2 links:

CLSTN2 (HGNC:):

CLSTN2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 3-140403621-T-G is Benign according to our data. Variant chr3-140403621-T-G is described in ClinVar as [Benign]. Clinvar id is 782435.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0136 (2075/152352) while in subpopulation AFR AF= 0.0463 (1925/41582). AF 95% confidence interval is 0.0446. There are 37 homozygotes in gnomad4. There are 1017 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 37 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLSTN2	NM_022131.3 linkuse as main transcript	c.233-8T>G		splice_region_variant, intron_variant		ENST00000458420.7	NP_071414.2	Q9H4D0
CLSTN2	XM_017007022.3 linkuse as main transcript	c.158-8T>G		splice_region_variant, intron_variant			XP_016862511.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLSTN2	ENST00000458420.7 linkuse as main transcript	c.233-8T>G		splice_region_variant, intron_variant		1	NM_022131.3	ENSP00000402460.2		Q9H4D0
CLSTN2	ENST00000511524.1 linkuse as main transcript	n.421-8T>G		splice_region_variant, intron_variant		2

Frequencies

GnomAD3 genomes

AF:

0.0136

AC:

2075

AN:

152234

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0464

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00693

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.000309

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00370

AC:

895

AN:

242054

Hom.:

AF XY:

0.00264

AC XY:

345

AN XY:

130570

show subpopulations

Gnomad AFR exome

AF:

0.0459

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000702

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000228

Gnomad OTH exome

AF:

0.00171

GnomAD4 exome

AF:

0.00144

AC:

2092

AN:

1448226

Hom.:

Cov.:

AF XY:

0.00130

AC XY:

935

AN XY:

719088

show subpopulations

Gnomad4 AFR exome

AF:

0.0454

Gnomad4 AMR exome

AF:

0.00371

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000166

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000184

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.0136

AC:

2075

AN:

152352

Hom.:

Cov.:

AF XY:

0.0137

AC XY:

1017

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0463

Gnomad4 AMR

AF:

0.00692

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000309

Gnomad4 OTH

AF:

0.00993

Alfa

AF:

0.00865

Hom.:

Bravo

AF:

0.0152

Asia WGS

AF:

0.00260

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

8.0

DANN

Benign

0.80

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0052

dbscSNV1_RF

Benign

0.084

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over