rs363223

Positions:

• chr10-117263050-G-A
• chr10-117263050-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003054.6(SLC18A2):​c.992-3683G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,046 control chromosomes in the GnomAD database, including 17,499 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 0.47 (17499 hom., cov: 32)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.657

Genes affected

SLC18A2 (HGNC:10935): (solute carrier family 18 member A2) This gene encodes an transmembrane protein that functions as an ATP-dependent transporter of monoamines, such as dopamine, norepinephrine, serotonin, and histamine. This protein transports amine neurotransmitters into synaptic vesicles. Polymorphisms in this gene may be associated with schizophrenia, bipolar disorder, and other neurological/psychiatric ailments. [provided by RefSeq, Jun 2018]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6	c.992-3683G>A		intron_variant		ENST00000644641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2	c.992-3683G>A		intron_variant			NM_003054.6	P1
SLC18A2	ENST00000497497.1	n.1408-3683G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71117 AN: 151928 Hom.: 17501 Cov.: 32

Gnomad AFR AF: 0.312

Gnomad AMI AF: 0.629

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.453

Gnomad SAS AF: 0.496

Gnomad FIN AF: 0.515

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.542

Gnomad OTH AF: 0.472

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

GnomAD4 genome AF: 0.468 AC: 71131 AN: 152046 Hom.: 17499 Cov.: 32 AF XY: 0.467 AC XY: 34671 AN XY: 74310

Gnomad4 AFR AF: 0.312

Gnomad4 AMR AF: 0.522

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.452

Gnomad4 SAS AF: 0.496

Gnomad4 FIN AF: 0.515

Gnomad4 NFE AF: 0.541

Gnomad4 OTH AF: 0.469

Alfa AF: 0.407 Hom.: 1692

Bravo AF: 0.466

Asia WGS AF: 0.454 AC: 1579 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	2.1
DANN	Benign	0.54

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: rs363223; hg19: chr10-119022561;