rs6554677

chr5-1236176-G-A

Variant summary

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

The NM_182632.3(SLC6A18):c.621+514G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 151,750 control chromosomes in the GnomAD database, including 1,488 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 0.12 (1488 hom., cov: 32)
• Consequence: SLC6A18 NM_182632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.250

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 (AFR) allele frequency at 95% confidence interval = 0.23 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A18	NM_182632.3	c.621+514G>A		intron_variant		ENST00000324642.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A18	ENST00000324642.4	c.621+514G>A		intron_variant		1	NM_182632.3	P1

Frequencies

GnomAD3 genomes AF: 0.118 AC: 17864 AN: 151634 Hom.: 1486 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.184

Gnomad AMR AF: 0.0816

Gnomad ASJ AF: 0.0432

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0578

Gnomad FIN AF: 0.131

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.0888

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

GnomAD4 genome AF: 0.118 AC: 17892 AN: 151750 Hom.: 1488 Cov.: 32 AF XY: 0.118 AC XY: 8754 AN XY: 74144

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.0816

Gnomad4 ASJ AF: 0.0432

Gnomad4 EAS AF: 0.000970

Gnomad4 SAS AF: 0.0570

Gnomad4 FIN AF: 0.131

Gnomad4 NFE AF: 0.0708

Gnomad4 OTH AF: 0.0878

Alfa AF: 0.102 Hom.: 420

Bravo AF: 0.122

Asia WGS AF: 0.0480 AC: 168 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	4.9
Dann	Benign	0.39

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: rs6554677; hg19: chr5-1236291;