8-20183201-T-C

Variant names:

• chr8-20183201-T-C
• rs1390939
• ENST00000440926.3:c.-466A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 8 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000440926.3. 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
	SLC18A1	NM_003053.4	MANE Select	c.-262A>G		upstream_gene	N/A	NP_003044.1	P54219-1
	SLC18A1	NM_001135691.3		c.-466A>G		upstream_gene	N/A	NP_001129163.1	P54219-1
	SLC18A1	NM_001438745.1		c.-262A>G		upstream_gene	N/A	NP_001425674.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A1	ENST00000440926.3	TSL:5	c.-466A>G		5_prime_UTR	Exon 1 of 17	ENSP00000387549.1	P54219-1
	SLC18A1	ENST00000437980.3	TSL:5	c.-466A>G		5_prime_UTR	Exon 1 of 16	ENSP00000413361.1	P54219-2
	SLC18A1	ENST00000276373.10	TSL:1 MANE Select	c.-262A>G		upstream_gene	N/A	ENSP00000276373.5	P54219-1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.250 AC: 2 AN: 8

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.639 AC: 23 AN: 36

Other (OTH) AC: 0 AN: 0

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

African (AFR) AF: 0.185 AC: 7671 AN: 41508

American (AMR) AF: 0.337 AC: 5142 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.515 AC: 1788 AN: 3470

East Asian (EAS) AF: 0.186 AC: 963 AN: 5166

South Asian (SAS) AF: 0.425 AC: 2048 AN: 4818

European-Finnish (FIN) AF: 0.590 AC: 6233 AN: 10570

Middle Eastern (MID) AF: 0.466 AC: 137 AN: 294

European-Non Finnish (NFE) AF: 0.551 AC: 37453 AN: 67968

Other (OTH) AF: 0.435 AC: 915 AN: 2104

Alfa AF: 0.506 Hom.: 83786

Bravo AF: 0.386

Asia WGS AF: 0.332 AC: 1159 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.6
DANN	Benign	0.49
PhyloP100		-0.19
PromoterAI		0.049	Neutral
Mutation Taster		=299/1	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1390939; hg19: chr8-20040712;