20-46024468-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001134771.2(SLC12A5):​c.121+2582C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.315 in 152,050 control chromosomes in the GnomAD database, including 8,278 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 0.31 ( 8278 hom., cov: 32)

Consequence

SLC12A5
NM_001134771.2 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.903
Variant links:
Genes affected
SLC12A5 (HGNC:13818): (solute carrier family 12 member 5) K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.96).
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.465 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC12A5NM_001134771.2 linkuse as main transcriptc.121+2582C>G intron_variant NP_001128243.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC12A5ENST00000454036.6 linkuse as main transcriptc.121+2582C>G intron_variant 5 ENSP00000387694 P3Q9H2X9-1
SLC12A5ENST00000428198.1 linkuse as main transcriptn.111+2582C>G intron_variant, non_coding_transcript_variant 3

Frequencies

GnomAD3 genomes
AF:
0.315
AC:
47846
AN:
151932
Hom.:
8270
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.470
Gnomad AMI
AF:
0.288
Gnomad AMR
AF:
0.285
Gnomad ASJ
AF:
0.226
Gnomad EAS
AF:
0.372
Gnomad SAS
AF:
0.407
Gnomad FIN
AF:
0.226
Gnomad MID
AF:
0.199
Gnomad NFE
AF:
0.237
Gnomad OTH
AF:
0.277
We have no GnomAD4 exomes data on this position. Probably position not covered by the project.
GnomAD4 genome
AF:
0.315
AC:
47887
AN:
152050
Hom.:
8278
Cov.:
32
AF XY:
0.316
AC XY:
23492
AN XY:
74332
show subpopulations
Gnomad4 AFR
AF:
0.470
Gnomad4 AMR
AF:
0.285
Gnomad4 ASJ
AF:
0.226
Gnomad4 EAS
AF:
0.372
Gnomad4 SAS
AF:
0.405
Gnomad4 FIN
AF:
0.226
Gnomad4 NFE
AF:
0.237
Gnomad4 OTH
AF:
0.279
Alfa
AF:
0.275
Hom.:
792
Bravo
AF:
0.324
Asia WGS
AF:
0.365
AC:
1267
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.96
CADD
Benign
0.64
DANN
Benign
0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs6094238; hg19: chr20-44653107; API