8-20147130-T-C

Variant names:

• chr8-20147130-T-C
• rs6586896
• NM_003053.4:c.1464+128A>G

Variant summary

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

The NM_003053.4(SLC18A1):​c.1464+128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0908 in 996,070 control chromosomes in the GnomAD database, including 4,719 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 0.069 (474 hom., cov: 32)
  • Exomes 𝑓: 0.095 (4245 hom.)
• Consequence: SLC18A1 NM_003053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573
• 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0977 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.1464+128A>G		intron	N/A	NP_003044.1	P54219-1
	SLC18A1	NM_001135691.3		c.1464+128A>G		intron	N/A	NP_001129163.1	P54219-1
	SLC18A1	NM_001438745.1		c.1380+128A>G		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.1464+128A>G		intron	N/A	ENSP00000276373.5	P54219-1
	SLC18A1	ENST00000265808.11	TSL:1	c.1368+128A>G		intron	N/A	ENSP00000265808.7	P54219-3
	SLC18A1	ENST00000440926.3	TSL:5	c.1464+128A>G		intron	N/A	ENSP00000387549.1	P54219-1

Frequencies

GnomAD3 genomes AF: 0.0695 AC: 10559 AN: 151902 Hom.: 474 Cov.: 32

Gnomad AFR AF: 0.0283

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0558

Gnomad ASJ AF: 0.0767

Gnomad EAS AF: 0.0549

Gnomad SAS AF: 0.0172

Gnomad FIN AF: 0.0777

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0998

Gnomad OTH AF: 0.0723

GnomAD4 exome AF: 0.0947 AC: 79899 AN: 844050 Hom.: 4245 AF XY: 0.0927 AC XY: 39001 AN XY: 420828

African (AFR) AF: 0.0248 AC: 495 AN: 19980

American (AMR) AF: 0.0453 AC: 684 AN: 15088

Ashkenazi Jewish (ASJ) AF: 0.0704 AC: 1078 AN: 15306

East Asian (EAS) AF: 0.0419 AC: 1327 AN: 31670

South Asian (SAS) AF: 0.0154 AC: 690 AN: 44690

European-Finnish (FIN) AF: 0.0866 AC: 3042 AN: 35124

Middle Eastern (MID) AF: 0.0784 AC: 245 AN: 3126

European-Non Finnish (NFE) AF: 0.108 AC: 69051 AN: 640746

Other (OTH) AF: 0.0858 AC: 3287 AN: 38320

GnomAD4 genome AF: 0.0695 AC: 10559 AN: 152020 Hom.: 474 Cov.: 32 AF XY: 0.0669 AC XY: 4974 AN XY: 74316

African (AFR) AF: 0.0284 AC: 1176 AN: 41448

American (AMR) AF: 0.0557 AC: 851 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0767 AC: 266 AN: 3468

East Asian (EAS) AF: 0.0546 AC: 282 AN: 5164

South Asian (SAS) AF: 0.0174 AC: 84 AN: 4818

European-Finnish (FIN) AF: 0.0777 AC: 822 AN: 10580

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0997 AC: 6774 AN: 67950

Other (OTH) AF: 0.0716 AC: 151 AN: 2110

Alfa AF: 0.0898 Hom.: 1887

Bravo AF: 0.0677

Asia WGS AF: 0.0330 AC: 115 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	0.33
DANN	Benign	0.45
PhyloP100		-0.57
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: rs6586896; hg19: chr8-20004641;