5-128098106-A-G

Variant summary

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

The NM_001046.3(SLC12A2):c.756+13396A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.825 in 152,042 control chromosomes in the GnomAD database, including 52,376 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 0.82 (52376 hom., cov: 32)
• Consequence: SLC12A2 NM_001046.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.731

Genes affected

SLC12A2 (HGNC:10911): (solute carrier family 12 member 2) The protein encoded by this gene mediates sodium and chloride transport and reabsorption. The encoded protein is a membrane protein and is important in maintaining proper ionic balance and cell volume. This protein is phosphorylated in response to DNA damage. Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.946 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC12A2	NM_001046.3	c.756+13396A>G		intron_variant		ENST00000262461.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC12A2	ENST00000262461.7	c.756+13396A>G		intron_variant		1	NM_001046.3	P4
SLC12A2	ENST00000343225.4	c.756+13396A>G		intron_variant		1		A2
SLC12A2	ENST00000509205.5	c.756+13396A>G		intron_variant, NMD_transcript_variant		1
SLC12A2	ENST00000628403.2	c.756+13396A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.824 AC: 125252 AN: 151924 Hom.: 52302 Cov.: 32

Gnomad AFR AF: 0.954

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.818

Gnomad ASJ AF: 0.725

Gnomad EAS AF: 0.625

Gnomad SAS AF: 0.692

Gnomad FIN AF: 0.866

Gnomad MID AF: 0.807

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.792

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

GnomAD4 genome AF: 0.825 AC: 125384 AN: 152042 Hom.: 52376 Cov.: 32 AF XY: 0.826 AC XY: 61417 AN XY: 74320

Gnomad4 AFR AF: 0.954

Gnomad4 AMR AF: 0.818

Gnomad4 ASJ AF: 0.725

Gnomad4 EAS AF: 0.625

Gnomad4 SAS AF: 0.695

Gnomad4 FIN AF: 0.866

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.791

Alfa AF: 0.785 Hom.: 22040

Bravo AF: 0.828

Asia WGS AF: 0.697 AC: 2421 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
Cadd	Benign	2.5
Dann	Benign	0.46

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: rs1112956; hg19: chr5-127433798;