rs1497020

Variant names:

• chr8-20144915-G-A
• rs1497020
• NM_003053.4:c.*848C>T

Variant summary

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

The NM_003053.4(SLC18A1):​c.*848C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.748 in 152,098 control chromosomes in the GnomAD database, including 43,560 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 0.75 (43560 hom., cov: 31)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SLC18A1 NM_003053.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.759
• Publications: 9 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.91 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A1	NM_003053.4	c.*848C>T		3_prime_UTR_variant	Exon 16 of 16	ENST00000276373.10	NP_003044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A1	ENST00000276373.10	c.*848C>T		3_prime_UTR_variant	Exon 16 of 16	1	NM_003053.4	ENSP00000276373.5

Frequencies

GnomAD3 genomes AF: 0.748 AC: 113638 AN: 151978 Hom.: 43515 Cov.: 31

Gnomad AFR AF: 0.918

Gnomad AMI AF: 0.594

Gnomad AMR AF: 0.678

Gnomad ASJ AF: 0.766

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.624

Gnomad FIN AF: 0.711

Gnomad MID AF: 0.763

Gnomad NFE AF: 0.690

Gnomad OTH AF: 0.748

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

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) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.500 AC: 1 AN: 2

GnomAD4 genome AF: 0.748 AC: 113743 AN: 152096 Hom.: 43560 Cov.: 31 AF XY: 0.743 AC XY: 55192 AN XY: 74330

African (AFR) AF: 0.918 AC: 38124 AN: 41520

American (AMR) AF: 0.678 AC: 10359 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.766 AC: 2661 AN: 3472

East Asian (EAS) AF: 0.555 AC: 2854 AN: 5146

South Asian (SAS) AF: 0.623 AC: 3009 AN: 4826

European-Finnish (FIN) AF: 0.711 AC: 7506 AN: 10554

Middle Eastern (MID) AF: 0.755 AC: 222 AN: 294

European-Non Finnish (NFE) AF: 0.690 AC: 46884 AN: 67966

Other (OTH) AF: 0.748 AC: 1582 AN: 2116

Alfa AF: 0.707 Hom.: 67169

Bravo AF: 0.755

Asia WGS AF: 0.646 AC: 2250 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.26
DANN	Benign	0.25
PhyloP100		-0.76
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: rs1497020; hg19: chr8-20002426;