rs1390939

Positions:

• chr8-20183201-T-C
• chr8-20183201-T-G

Variant summary

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

The ENST00000440926.3(SLC18A1):​c.-466A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.413 in 152,126 control chromosomes in the GnomAD database, including 15,134 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 0.41 (15125 hom., cov: 32)
  • Exomes 𝑓: 0.57 (9 hom.)
• Consequence: SLC18A1 ENST00000440926.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.190

Genes affected

SLC18A1 (HGNC:10934): (solute carrier family 18 member A1) The vesicular monoamine transporter acts to accumulate cytosolic monoamines into vesicles, using the proton gradient maintained across the vesicular membrane. Its proper function is essential to the correct activity of the monoaminergic systems that have been implicated in several human neuropsychiatric disorders. The transporter is a site of action of important drugs, including reserpine and tetrabenazine (Peter et al., 1993 [PubMed 7905859]). See also SLC18A2 (MIM 193001).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.546 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC18A1	ENST00000437980.3	c.-466A>G		5_prime_UTR_variant	1/16	5		ENSP00000413361
SLC18A1	ENST00000440926.3	c.-466A>G		5_prime_UTR_variant	1/17	5		ENSP00000387549	P1
SLC18A1	ENST00000519026.5			upstream_gene_variant		5		ENSP00000429664

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62832 AN: 151964 Hom.: 15120 Cov.: 32

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.337

Gnomad ASJ AF: 0.515

Gnomad EAS AF: 0.186

Gnomad SAS AF: 0.423

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.433

GnomAD4 exome AF: 0.568 AC: 25 AN: 44 Hom.: 9 Cov.: 0 AF XY: 0.692 AC XY: 18 AN XY: 26

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.639

GnomAD4 genome AF: 0.413 AC: 62856 AN: 152082 Hom.: 15125 Cov.: 32 AF XY: 0.412 AC XY: 30661 AN XY: 74356

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.337

Gnomad4 ASJ AF: 0.515

Gnomad4 EAS AF: 0.186

Gnomad4 SAS AF: 0.425

Gnomad4 FIN AF: 0.590

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.435

Alfa AF: 0.526 Hom.: 41971

Bravo AF: 0.386

Asia WGS AF: 0.332 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.49

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: rs1390939; hg19: chr8-20040712;