rs4975625

Positions:

• chr5-1228100-G-A
• chr5-1228100-G-C

Variant summary

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

The NM_182632.3(SLC6A18):​c.160+2463G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,858 control chromosomes in the GnomAD database, including 11,925 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 0.39 (11925 hom., cov: 33)
• Consequence: SLC6A18 NM_182632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14

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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.427 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A18	NM_182632.3	c.160+2463G>A		intron_variant		ENST00000324642.4	NP_872438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A18	ENST00000324642.4	c.160+2463G>A		intron_variant		1	NM_182632.3	ENSP00000323549	P1
SLC6A18	ENST00000513607.2	n.229+2463G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.393 AC: 59681 AN: 151740 Hom.: 11913 Cov.: 33

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.341

Gnomad AMR AF: 0.422

Gnomad ASJ AF: 0.354

Gnomad EAS AF: 0.234

Gnomad SAS AF: 0.347

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.431

Gnomad OTH AF: 0.393

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

GnomAD4 genome AF: 0.393 AC: 59729 AN: 151858 Hom.: 11925 Cov.: 33 AF XY: 0.391 AC XY: 29035 AN XY: 74202

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.354

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.431

Gnomad4 OTH AF: 0.388

Alfa AF: 0.409 Hom.: 6262

Bravo AF: 0.392

Asia WGS AF: 0.305 AC: 1059 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.1
DANN	Benign	0.56

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: rs4975625; hg19: chr5-1228215;