Genetic Variant SLC6A18:c.301+17G>C (chr5-1232376-G-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

Publications

8 publications found

Variant links:

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]

SLC6A18 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SLC6A18	NM_182632.3 link	c.301+17G>C		intron_variant	Intron 2 of 11	ENST00000324642.4	NP_872438.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A18	ENST00000324642.4 link	c.301+17G>C		intron_variant	Intron 2 of 11	1	NM_182632.3	ENSP00000323549.3
SLC6A18	ENST00000513607.2 link	n.370+17G>C		intron_variant	Intron 2 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.906

AC:

137814

AN:

152170

Hom.:

62788

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.878

AC:

205281

AN:

233924

AF XY:

0.879

show subpopulations

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 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.:

AF XY:

0.903

AC XY:

650940

AN XY:

720588

show subpopulations

African (AFR)

AF:

0.947

AC:

31607

AN:

33360

American (AMR)

AF:

0.836

AC:

36529

AN:

43696

Ashkenazi Jewish (ASJ)

AF:

0.942

AC:

24343

AN:

25830

East Asian (EAS)

AF:

0.679

AC:

26745

AN:

39366

South Asian (SAS)

AF:

0.832

AC:

69975

AN:

84148

European-Finnish (FIN)

AF:

0.931

AC:

48196

AN:

51774

Middle Eastern (MID)

AF:

0.914

AC:

4347

AN:

4758

European-Non Finnish (NFE)

AF:

0.919

AC:

1017901

AN:

1108206

Other (OTH)

AF:

0.895

AC:

53636

AN:

59922

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

6735

13470

20204

26939

33674

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

21422

42844

64266

85688

107110

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.906

AC:

137927

AN:

152288

Hom.:

62837

Cov.:

AF XY:

0.901

AC XY:

67111

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.943

AC:

39204

AN:

41564

American (AMR)

AF:

0.842

AC:

12889

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.947

AC:

3285

AN:

3470

East Asian (EAS)

AF:

0.606

AC:

3130

AN:

5168

South Asian (SAS)

AF:

0.817

AC:

3934

AN:

4818

European-Finnish (FIN)

AF:

0.929

AC:

9867

AN:

10618

Middle Eastern (MID)

AF:

0.922

AC:

271

AN:

294

European-Non Finnish (NFE)

AF:

0.921

AC:

62669

AN:

68026

Other (OTH)

AF:

0.914

AC:

1931

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

691

1382

2074

2765

3456

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

902

1804

2706

3608

4510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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

(source)

DANN

Benign

0.27

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over