8-20178722-T-G

Variant names:

• chr8-20178722-T-G
• rs2279709
• NM_003053.4:c.489-229A>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003053.4(SLC18A1):​c.489-229A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.51 in 151,952 control chromosomes in the GnomAD database, including 20,233 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 0.51 (20233 hom., cov: 31)
• Consequence: SLC18A1 NM_003053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.49
• 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.563 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A1	NM_003053.4	c.489-229A>C		intron_variant	Intron 3 of 15	ENST00000276373.10	NP_003044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A1	ENST00000276373.10	c.489-229A>C		intron_variant	Intron 3 of 15	1	NM_003053.4	ENSP00000276373.5

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77378 AN: 151834 Hom.: 20219 Cov.: 31

Gnomad AFR AF: 0.439

Gnomad AMI AF: 0.559

Gnomad AMR AF: 0.424

Gnomad ASJ AF: 0.550

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.521

Gnomad FIN AF: 0.607

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.509

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

GnomAD4 genome AF: 0.510 AC: 77430 AN: 151952 Hom.: 20233 Cov.: 31 AF XY: 0.508 AC XY: 37745 AN XY: 74254

African (AFR) AF: 0.439 AC: 18177 AN: 41448

American (AMR) AF: 0.424 AC: 6473 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.550 AC: 1907 AN: 3468

East Asian (EAS) AF: 0.323 AC: 1663 AN: 5150

South Asian (SAS) AF: 0.523 AC: 2515 AN: 4810

European-Finnish (FIN) AF: 0.607 AC: 6404 AN: 10552

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.568 AC: 38563 AN: 67942

Other (OTH) AF: 0.510 AC: 1077 AN: 2110

Alfa AF: 0.517 Hom.: 3315

Bravo AF: 0.491

Asia WGS AF: 0.470 AC: 1640 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.64
DANN	Benign	0.76
PhyloP100		-1.5
Mutation Taster		=100/0	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: rs2279709; hg19: chr8-20036233;