dbSNP rs7801190: SLC12A9:c.1218+239C>G (chr7-100860471-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_020246.4(SLC12A9):c.1218+239C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0645 in 551,228 control chromosomes in the GnomAD database, including 2,107 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 0.096 ( 1247 hom., cov: 33)

Exomes 𝑓: 0.053 ( 860 hom. )

Consequence

SLC12A9
NM_020246.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.700

Publications

24 publications found

Variant links:

Genes affected

SLC12A9 (HGNC:17435): (solute carrier family 12 member 9) Predicted to enable potassium:chloride symporter activity. Predicted to be involved in cell volume homeostasis; inorganic ion homeostasis; and inorganic ion transmembrane transport. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

SLC12A9 Gene-Disease associations (from GenCC):

neurodevelopmental disorder
Inheritance: AR Classification: STRONG Submitted by: PanelApp Australia
complex neurodevelopmental disorder
Inheritance: AR Classification: MODERATE, LIMITED Submitted by: G2P, Ambry Genetics

SLC12A9 links:

Genome browser will be placed here

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=-0.88).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020246.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC12A9	NM_020246.4	MANE Select	c.1218+239C>G	intron	N/A	NP_064631.2
SLC12A9	NM_001363493.2		c.1218+239C>G	intron	N/A	NP_001350422.1	Q9BXP2-1
SLC12A9	NM_001363494.1		c.789+239C>G	intron	N/A	NP_001350423.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC12A9	ENST00000354161.8	TSL:1 MANE Select	c.1218+239C>G	intron	N/A	ENSP00000275730.4	Q9BXP2-1
SLC12A9	ENST00000415287.5	TSL:1	c.951+239C>G	intron	N/A	ENSP00000413796.1	Q9BXP2-2
SLC12A9	ENST00000971215.1		c.1305+152C>G	intron	N/A	ENSP00000641274.1

Frequencies

GnomAD3 genomes

AF:

0.0958

AC:

14530

AN:

151656

Hom.:

1241

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.00769

Gnomad AMR

AF:

0.0618

Gnomad ASJ

AF:

0.0989

Gnomad EAS

AF:

0.000585

Gnomad SAS

AF:

0.0614

Gnomad FIN

AF:

0.0295

Gnomad MID

AF:

0.0994

Gnomad NFE

AF:

0.0462

Gnomad OTH

AF:

0.0985

GnomAD4 exome

AF:

0.0525

AC:

20977

AN:

399454

Hom.:

860

Cov.:

AF XY:

0.0536

AC XY:

11249

AN XY:

210060

show subpopulations

African (AFR)

AF:

0.216

AC:

2471

AN:

11442

American (AMR)

AF:

0.0516

AC:

697

AN:

13510

Ashkenazi Jewish (ASJ)

AF:

0.0987

AC:

1230

AN:

12464

East Asian (EAS)

AF:

0.000260

AC:

AN:

26962

South Asian (SAS)

AF:

0.0627

AC:

2538

AN:

40456

European-Finnish (FIN)

AF:

0.0301

AC:

779

AN:

25852

Middle Eastern (MID)

AF:

0.103

AC:

203

AN:

1964

European-Non Finnish (NFE)

AF:

0.0476

AC:

11605

AN:

243638

Other (OTH)

AF:

0.0625

AC:

1447

AN:

23166

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

917

1834

2752

3669

4586

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<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:

0.0960

AC:

14563

AN:

151774

Hom.:

1247

Cov.:

AF XY:

0.0935

AC XY:

6930

AN XY:

74152

show subpopulations

African (AFR)

AF:

0.225

AC:

9294

AN:

41340

American (AMR)

AF:

0.0615

AC:

938

AN:

15246

Ashkenazi Jewish (ASJ)

AF:

0.0989

AC:

343

AN:

3468

East Asian (EAS)

AF:

0.000586

AC:

AN:

5116

South Asian (SAS)

AF:

0.0611

AC:

293

AN:

4798

European-Finnish (FIN)

AF:

0.0295

AC:

312

AN:

10562

Middle Eastern (MID)

AF:

0.100

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0462

AC:

3139

AN:

67930

Other (OTH)

AF:

0.0970

AC:

205

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

624

1248

1871

2495

3119

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

152

304

456

608

760

<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:

0.0555

Hom.:

182

Bravo

AF:

0.103

Asia WGS

AF:

0.0400

AC:

140

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

2.5

(source)

DANN

Benign

0.54

PhyloP100

-0.70

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over