rs1034969

Variant names:

• chr12-6464690-G-A
• rs1034969
• ENST00000538970.5:n.459C>T

Your query was ambiguous. Multiple possible variants found:

• chr12-6464690-G-A
• chr12-6464690-G-T

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BS1

The NM_014231.5(VAMP1):​c.340+200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000127 in 1,492,240 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000013 (0 hom.)
• Consequence: VAMP1 NM_014231.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.148
• Publications: 18 publications found

Genes affected

VAMP1 (HGNC:12642): (vesicle associated membrane protein 1) Synapotobrevins, syntaxins, and the synaptosomal-associated protein SNAP25 are the main components of a protein complex involved in the docking and/or fusion of synaptic vesicles with the presynaptic membrane. The protein encoded by this gene is a member of the vesicle-associated membrane protein (VAMP)/synaptobrevin family. Mutations in this gene are associated with autosomal dominant spastic ataxia 1. Multiple alternative splice variants have been described, but the full-length nature of some variants has not been defined. [provided by RefSeq, Jul 2014]

TAPBPL (HGNC:30683): (TAP binding protein like) Tapasin, or TAPBP (MIM 601962), is a member of the variable-constant Ig superfamily that links major histocompatibility complex (MHC) class I molecules to the transporter associated with antigen processing (TAP; see MIM 170260) in the endoplasmic reticulum (ER). The TAPBP gene is located near the MHC complex on chromosome 6p21.3. TAPBPL is a member of the Ig superfamily that is localized on chromosome 12p13.3, a region somewhat paralogous to the MHC.[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.0000134 (18/1340370) while in subpopulation EAS AF = 0.000346 (13/37518). AF 95% confidence interval is 0.000204. There are 0 homozygotes in GnomAdExome4. There are 11 alleles in the male GnomAdExome4 subpopulation. Median coverage is 34. This position passed quality control check.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
VAMP1	NM_014231.5	c.340+200C>T		intron_variant	Intron 4 of 4	ENST00000396308.4	NP_055046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
VAMP1	ENST00000396308.4	c.340+200C>T		intron_variant	Intron 4 of 4	2	NM_014231.5	ENSP00000379602.3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151870 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000134 AC: 18 AN: 1340370 Hom.: 0 Cov.: 34 AF XY: 0.0000168 AC XY: 11 AN XY: 656182

African (AFR) AF: 0.00 AC: 0 AN: 29500

American (AMR) AF: 0.00 AC: 0 AN: 24004

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19464

East Asian (EAS) AF: 0.000347 AC: 13 AN: 37518

South Asian (SAS) AF: 0.0000444 AC: 3 AN: 67514

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43208

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3856

European-Non Finnish (NFE) AF: 0.00000189 AC: 2 AN: 1059892

Other (OTH) AF: 0.00 AC: 0 AN: 55414

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151870 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 74128

African (AFR) AF: 0.0000242 AC: 1 AN: 41324

American (AMR) AF: 0.00 AC: 0 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5156

South Asian (SAS) AF: 0.00 AC: 0 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 24132

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.93
PhyloP100		0.15
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1034969; hg19: chr12-6573856;