chr8-20164494-G-C

Variant names:

• chr8-20164494-G-C
• rs3735835
• NM_003053.4:c.1015+375C>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.1015+375C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,000 control chromosomes in the GnomAD database, including 12,003 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 0.38 (12003 hom., cov: 32)
• Consequence: SLC18A1 NM_003053.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.300
• Publications: 1 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=-0.76).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.467 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC18A1	NM_003053.4	c.1015+375C>G		intron_variant	Intron 10 of 15	ENST00000276373.10	NP_003044.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC18A1	ENST00000276373.10	c.1015+375C>G		intron_variant	Intron 10 of 15	1	NM_003053.4	ENSP00000276373.5

Frequencies

GnomAD3 genomes AF: 0.381 AC: 57795 AN: 151882 Hom.: 11999 Cov.: 32

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.499

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.534

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.358

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.560

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.380 AC: 57830 AN: 152000 Hom.: 12003 Cov.: 32 AF XY: 0.375 AC XY: 27866 AN XY: 74286

African (AFR) AF: 0.235 AC: 9755 AN: 41462

American (AMR) AF: 0.360 AC: 5506 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 1851 AN: 3468

East Asian (EAS) AF: 0.260 AC: 1335 AN: 5142

South Asian (SAS) AF: 0.359 AC: 1732 AN: 4822

European-Finnish (FIN) AF: 0.392 AC: 4141 AN: 10564

Middle Eastern (MID) AF: 0.554 AC: 163 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 32005 AN: 67946

Other (OTH) AF: 0.421 AC: 889 AN: 2110

Alfa AF: 0.400 Hom.: 1558

Bravo AF: 0.377

Asia WGS AF: 0.355 AC: 1234 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.6
DANN	Benign	0.81
PhyloP100		-0.30
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: rs3735835; hg19: chr8-20022005;