5-128137438-T-C

Position:

• chr5-128137438-T-C

Variant summary

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

The NM_001046.3(SLC12A2):​c.1409-1159T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.101 in 152,208 control chromosomes in the GnomAD database, including 1,129 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 0.10 (1129 hom., cov: 32)
• Consequence: SLC12A2 NM_001046.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.64

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]

SLC12A2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC12A2	NM_001046.3	c.1409-1159T>C		intron_variant		ENST00000262461.7	NP_001037.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC12A2	ENST00000262461.7	c.1409-1159T>C		intron_variant		1	NM_001046.3	ENSP00000262461.2
SLC12A2	ENST00000343225.4	c.1409-1159T>C		intron_variant		1		ENSP00000340878.4
SLC12A2	ENST00000509205.5	n.1409-1159T>C		intron_variant		1		ENSP00000427109.1
SLC12A2	ENST00000628403.2	c.1409-1159T>C		intron_variant		5		ENSP00000486323.1

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15329 AN: 152090 Hom.: 1123 Cov.: 32

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.0724

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.157

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.104

Gnomad OTH AF: 0.105

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

GnomAD4 genome AF: 0.101 AC: 15339 AN: 152208 Hom.: 1129 Cov.: 32 AF XY: 0.106 AC XY: 7883 AN XY: 74406

Gnomad4 AFR AF: 0.0241

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.250

Gnomad4 SAS AF: 0.157

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.104

Gnomad4 OTH AF: 0.106

Alfa AF: 0.105 Hom.: 449

Bravo AF: 0.107

Asia WGS AF: 0.200 AC: 696 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	15
DANN	Benign	0.75

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: rs10519973; hg19: chr5-127473130;