8-20147130-T-C

Position:

• chr8-20147130-T-C

Variant summary

Our verdict is Benign. Variant got -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

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 = 0.0977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC18A1	NM_003053.4	c.1464+128A>G		intron_variant		ENST00000276373.10	NP_003044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC18A1	ENST00000276373.10	c.1464+128A>G		intron_variant		1	NM_003053.4	ENSP00000276373.5

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

Gnomad4 AFR exome AF: 0.0248

Gnomad4 AMR exome AF: 0.0453

Gnomad4 ASJ exome AF: 0.0704

Gnomad4 EAS exome AF: 0.0419

Gnomad4 SAS exome AF: 0.0154

Gnomad4 FIN exome AF: 0.0866

Gnomad4 NFE exome AF: 0.108

Gnomad4 OTH exome AF: 0.0858

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

Gnomad4 AFR AF: 0.0284

Gnomad4 AMR AF: 0.0557

Gnomad4 ASJ AF: 0.0767

Gnomad4 EAS AF: 0.0546

Gnomad4 SAS AF: 0.0174

Gnomad4 FIN AF: 0.0777

Gnomad4 NFE AF: 0.0997

Gnomad4 OTH AF: 0.0716

Alfa AF: 0.0882 Hom.: 902

Bravo AF: 0.0677

Asia WGS AF: 0.0330 AC: 115 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	0.33
DANN	Benign	0.45

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: rs6586896; hg19: chr8-20004641;