5-1232376-G-C

Position:

• chr5-1232376-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.301+17G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.905 in 1,603,348 control chromosomes in the GnomAD database, including 659,199 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 0.91 (62837 hom., cov: 34)
  • Exomes 𝑓: 0.91 (596362 hom.)
• Consequence: SLC6A18 NM_182632.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.77

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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.935 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A18	NM_182632.3	c.301+17G>C		intron_variant		ENST00000324642.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A18	ENST00000324642.4	c.301+17G>C		intron_variant		1	NM_182632.3	P1
SLC6A18	ENST00000513607.2	n.370+17G>C		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137814 AN: 152170 Hom.: 62788 Cov.: 34

Gnomad AFR AF: 0.943

Gnomad AMI AF: 0.819

Gnomad AMR AF: 0.842

Gnomad ASJ AF: 0.947

Gnomad EAS AF: 0.606

Gnomad SAS AF: 0.815

Gnomad FIN AF: 0.929

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.913

GnomAD3 exomes AF: 0.878 AC: 205281 AN: 233924 Hom.: 91025 AF XY: 0.879 AC XY: 111524 AN XY: 126918

Gnomad AFR exome AF: 0.945

Gnomad AMR exome AF: 0.833

Gnomad ASJ exome AF: 0.944

Gnomad EAS exome AF: 0.611

Gnomad SAS exome AF: 0.834

Gnomad FIN exome AF: 0.929

Gnomad NFE exome AF: 0.921

Gnomad OTH exome AF: 0.901

GnomAD4 exome AF: 0.905 AC: 1313279 AN: 1451060 Hom.: 596362 Cov.: 58 AF XY: 0.903 AC XY: 650940 AN XY: 720588

Gnomad4 AFR exome AF: 0.947

Gnomad4 AMR exome AF: 0.836

Gnomad4 ASJ exome AF: 0.942

Gnomad4 EAS exome AF: 0.679

Gnomad4 SAS exome AF: 0.832

Gnomad4 FIN exome AF: 0.931

Gnomad4 NFE exome AF: 0.919

Gnomad4 OTH exome AF: 0.895

GnomAD4 genome AF: 0.906 AC: 137927 AN: 152288 Hom.: 62837 Cov.: 34 AF XY: 0.901 AC XY: 67111 AN XY: 74456

Gnomad4 AFR AF: 0.943

Gnomad4 AMR AF: 0.842

Gnomad4 ASJ AF: 0.947

Gnomad4 EAS AF: 0.606

Gnomad4 SAS AF: 0.817

Gnomad4 FIN AF: 0.929

Gnomad4 NFE AF: 0.921

Gnomad4 OTH AF: 0.914

Alfa AF: 0.923 Hom.: 6912

Bravo AF: 0.902

Asia WGS AF: 0.769 AC: 2677 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.0
DANN	Benign	0.27

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4975623; hg19: chr5-1232491;