1-9794180-A-G

Position:

• chr1-9794180-A-G

Variant summary

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

The NM_001009566.3(CLSTN1):​c.92-20786T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.921 in 151,374 control chromosomes in the GnomAD database, including 64,520 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 0.92 (64520 hom., cov: 32)
• Consequence: CLSTN1 NM_001009566.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.12

Genes affected

CLSTN1 (HGNC:17447): (calsyntenin 1) This gene is a member of the calsyntenin family, a subset of the cadherin superfamily. The encoded transmembrane protein, also known as alcadein-alpha, is thought to bind to kinesin-1 motors to mediate the axonal anterograde transport of certain types of vesicle. Amyloid precursor protein (APP) is trafficked via these vesicles and so this protein is being investigated to see how it might contribute to the mechanisms underlying Alzheimer's disease. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2014]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CLSTN1	NM_001009566.3	c.92-20786T>C		intron_variant		ENST00000377298.9	NP_001009566.1
CLSTN1	NM_014944.4	c.92-20786T>C		intron_variant			NP_055759.3
CLSTN1	NM_001302883.1	c.92-20786T>C		intron_variant			NP_001289812.1
CLSTN1	XM_047449470.1	c.92-20786T>C		intron_variant			XP_047305426.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CLSTN1	ENST00000377298.9	c.92-20786T>C		intron_variant		1	NM_001009566.3	ENSP00000366513.4
CLSTN1	ENST00000361311.4	c.92-20786T>C		intron_variant		1		ENSP00000354997.4
CLSTN1	ENST00000650348.1	n.26-20786T>C		intron_variant				ENSP00000497950.1

Frequencies

GnomAD3 genomes AF: 0.921 AC: 139271 AN: 151262 Hom.: 64467 Cov.: 32

Gnomad AFR AF: 0.978

Gnomad AMI AF: 0.956

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.889

Gnomad EAS AF: 0.961

Gnomad SAS AF: 0.855

Gnomad FIN AF: 0.949

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.901

Gnomad OTH AF: 0.909

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

GnomAD4 genome AF: 0.921 AC: 139380 AN: 151374 Hom.: 64520 Cov.: 32 AF XY: 0.921 AC XY: 68028 AN XY: 73854

Gnomad4 AFR AF: 0.978

Gnomad4 AMR AF: 0.847

Gnomad4 ASJ AF: 0.889

Gnomad4 EAS AF: 0.961

Gnomad4 SAS AF: 0.854

Gnomad4 FIN AF: 0.949

Gnomad4 NFE AF: 0.901

Gnomad4 OTH AF: 0.910

Alfa AF: 0.905 Hom.: 61652

Bravo AF: 0.916

Asia WGS AF: 0.905 AC: 3096 AN: 3418

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.69
DANN	Benign	0.34

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: rs2119508; hg19: chr1-9854238;