8-20175076-G-T

Variant names:

• chr8-20175076-G-T
• rs952859
• NM_003053.4:c.548-632C>A

Variant summary

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

The NM_003053.4(SLC18A1):​c.548-632C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.767 in 152,140 control chromosomes in the GnomAD database, including 45,376 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 0.77 (45376 hom., cov: 32)
• Consequence: SLC18A1 NM_003053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.291
• Publications: 4 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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003053.4. 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.548-632C>A		intron	N/A	NP_003044.1	P54219-1
	SLC18A1	NM_001135691.3		c.548-632C>A		intron	N/A	NP_001129163.1	P54219-1
	SLC18A1	NM_001438745.1		c.548-1948C>A		intron	N/A	NP_001425674.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC18A1	ENST00000276373.10	TSL:1 MANE Select	c.548-632C>A		intron	N/A	ENSP00000276373.5	P54219-1
	SLC18A1	ENST00000265808.11	TSL:1	c.548-632C>A		intron	N/A	ENSP00000265808.7	P54219-3
	SLC18A1	ENST00000440926.3	TSL:5	c.548-632C>A		intron	N/A	ENSP00000387549.1	P54219-1

Frequencies

GnomAD3 genomes AF: 0.767 AC: 116569 AN: 152022 Hom.: 45321 Cov.: 32

Gnomad AFR AF: 0.885

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.609

Gnomad ASJ AF: 0.806

Gnomad EAS AF: 0.717

Gnomad SAS AF: 0.688

Gnomad FIN AF: 0.700

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.748

Gnomad OTH AF: 0.768

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

GnomAD4 genome AF: 0.767 AC: 116677 AN: 152140 Hom.: 45376 Cov.: 32 AF XY: 0.759 AC XY: 56431 AN XY: 74374

African (AFR) AF: 0.885 AC: 36764 AN: 41534

American (AMR) AF: 0.609 AC: 9303 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.806 AC: 2796 AN: 3470

East Asian (EAS) AF: 0.716 AC: 3708 AN: 5178

South Asian (SAS) AF: 0.688 AC: 3321 AN: 4824

European-Finnish (FIN) AF: 0.700 AC: 7385 AN: 10552

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.748 AC: 50840 AN: 67982

Other (OTH) AF: 0.770 AC: 1626 AN: 2112

Alfa AF: 0.747 Hom.: 50287

Bravo AF: 0.767

Asia WGS AF: 0.720 AC: 2505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.93
DANN	Benign	0.34
PhyloP100		-0.29
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: rs952859; hg19: chr8-20032587;