rs1010

Variant names:

• chr2-85581859-T-C
• rs1010
• NM_003761.5:c.*143T>C

Your query was ambiguous. Multiple possible variants found:

• chr2-85581859-T-C
• chr2-85581859-T-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003761.5(VAMP8):​c.*143T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 1,133,830 control chromosomes in the GnomAD database, including 95,968 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (15903 hom., cov: 30)
  • Exomes 𝑓: 0.40 (80065 hom.)
• Consequence: VAMP8 NM_003761.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0580
• Publications: 68 publications found

Genes affected

VAMP8 (HGNC:12647): (vesicle associated membrane protein 8) This gene encodes an integral membrane protein that belongs to the synaptobrevin/vesicle-associated membrane protein subfamily of soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs). The encoded protein is involved in the fusion of synaptic vesicles with the presynaptic membrane.[provided by RefSeq, Jun 2010]

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-85581859-T-C is Benign according to our data. Variant chr2-85581859-T-C is described in ClinVar as Benign. ClinVar VariationId is 1182311.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003761.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP8	NM_003761.5	MANE Select	c.*143T>C		3_prime_UTR	Exon 3 of 3	NP_003752.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	VAMP8	ENST00000263864.10	TSL:1 MANE Select	c.*143T>C		3_prime_UTR	Exon 3 of 3	ENSP00000263864.5	Q9BV40
	VAMP8	ENST00000409760.1	TSL:3	c.*279T>C		3_prime_UTR	Exon 4 of 4	ENSP00000387094.1	B8ZZT4
	VAMP8	ENST00000432071.1	TSL:3	c.*143T>C		3_prime_UTR	Exon 3 of 3	ENSP00000407984.1	C9JXZ5

Frequencies

GnomAD3 genomes AF: 0.451 AC: 68489 AN: 151694 Hom.: 15880 Cov.: 30

Gnomad AFR AF: 0.563

Gnomad AMI AF: 0.457

Gnomad AMR AF: 0.375

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.386

Gnomad SAS AF: 0.378

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.418

Gnomad OTH AF: 0.432

GnomAD4 exome AF: 0.402 AC: 395243 AN: 982016 Hom.: 80065 Cov.: 13 AF XY: 0.403 AC XY: 200056 AN XY: 496772

African (AFR) AF: 0.549 AC: 12420 AN: 22606

American (AMR) AF: 0.309 AC: 9073 AN: 29382

Ashkenazi Jewish (ASJ) AF: 0.366 AC: 6554 AN: 17928

East Asian (EAS) AF: 0.371 AC: 13722 AN: 36948

South Asian (SAS) AF: 0.370 AC: 23092 AN: 62468

European-Finnish (FIN) AF: 0.423 AC: 16474 AN: 38914

Middle Eastern (MID) AF: 0.370 AC: 1277 AN: 3448

European-Non Finnish (NFE) AF: 0.405 AC: 294310 AN: 726324

Other (OTH) AF: 0.416 AC: 18321 AN: 43998

GnomAD4 genome AF: 0.452 AC: 68561 AN: 151814 Hom.: 15903 Cov.: 30 AF XY: 0.450 AC XY: 33391 AN XY: 74186

African (AFR) AF: 0.563 AC: 23288 AN: 41380

American (AMR) AF: 0.374 AC: 5711 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1253 AN: 3468

East Asian (EAS) AF: 0.386 AC: 1987 AN: 5150

South Asian (SAS) AF: 0.379 AC: 1821 AN: 4808

European-Finnish (FIN) AF: 0.441 AC: 4636 AN: 10520

Middle Eastern (MID) AF: 0.364 AC: 107 AN: 294

European-Non Finnish (NFE) AF: 0.418 AC: 28425 AN: 67924

Other (OTH) AF: 0.435 AC: 917 AN: 2108

Alfa AF: 0.419 Hom.: 21461

Bravo AF: 0.452

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	5.5
DANN	Benign	0.36
PhyloP100		-0.058
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs1010; hg19: chr2-85808982; COSMIC: COSV55705317; COSMIC: COSV55705317;