rs929493

chr10-117259615-C-T

Variant summary

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

The NM_003054.6(SLC18A2):c.991+1723C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.704 in 152,134 control chromosomes in the GnomAD database, including 39,346 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 0.70 (39346 hom., cov: 33)
• Consequence: SLC18A2 NM_003054.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

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=-0.96).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC18A2	NM_003054.6	c.991+1723C>T		intron_variant		ENST00000644641.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC18A2	ENST00000644641.2	c.991+1723C>T		intron_variant			NM_003054.6	P1
SLC18A2	ENST00000497497.1	n.1407+1723C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.705 AC: 107142 AN: 152016 Hom.: 39351 Cov.: 33

Gnomad AFR AF: 0.519

Gnomad AMI AF: 0.763

Gnomad AMR AF: 0.700

Gnomad ASJ AF: 0.821

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.632

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.850

Gnomad NFE AF: 0.827

Gnomad OTH AF: 0.729

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

GnomAD4 genome AF: 0.704 AC: 107148 AN: 152134 Hom.: 39346 Cov.: 33 AF XY: 0.699 AC XY: 51974 AN XY: 74354

Gnomad4 AFR AF: 0.518

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.821

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.827

Gnomad4 OTH AF: 0.726

Alfa AF: 0.757 Hom.: 18329

Bravo AF: 0.687

Asia WGS AF: 0.474 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	0.73
Dann	Benign	0.37

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: rs929493; hg19: chr10-119019126;