rs34156553

Positions:

• chr5-1243130-C-T

Variant summary

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

The NM_182632.3(SLC6A18):​c.1131+267C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0441 in 152,224 control chromosomes in the GnomAD database, including 223 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 0.044 (223 hom., cov: 33)
• Consequence: SLC6A18 NM_182632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.758

Genes affected

SLC6A18 (HGNC:26441): (solute carrier family 6 member 18) The SLC6 family of proteins, which includes SLC6A18, act as specific transporters for neurotransmitters, amino acids, and osmolytes like betaine, taurine, and creatine. SLC6 proteins are sodium cotransporters that derive the energy for solute transport from the electrochemical gradient for sodium ions (Hoglund et al., 2005 [PubMed 16125675]).[supplied by OMIM, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.059 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A18	NM_182632.3	c.1131+267C>T		intron_variant		ENST00000324642.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A18	ENST00000324642.4	c.1131+267C>T		intron_variant		1	NM_182632.3	P1

Frequencies

GnomAD3 genomes AF: 0.0441 AC: 6708 AN: 152106 Hom.: 223 Cov.: 33

Gnomad AFR AF: 0.00939

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0513

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0282

Gnomad FIN AF: 0.0963

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0606

Gnomad OTH AF: 0.0397

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

GnomAD4 genome AF: 0.0441 AC: 6714 AN: 152224 Hom.: 223 Cov.: 33 AF XY: 0.0452 AC XY: 3360 AN XY: 74416

Gnomad4 AFR AF: 0.00936

Gnomad4 AMR AF: 0.0516

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.000774

Gnomad4 SAS AF: 0.0284

Gnomad4 FIN AF: 0.0963

Gnomad4 NFE AF: 0.0606

Gnomad4 OTH AF: 0.0393

Alfa AF: 0.0668 Hom.: 55

Bravo AF: 0.0407

Asia WGS AF: 0.0230 AC: 81 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.50

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: rs34156553; hg19: chr5-1243245;