5-128098106-A-G

Variant names:

• chr5-128098106-A-G
• rs1112956
• NM_001046.3:c.756+13396A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• Delpire-McNeill syndrome

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hearing loss, autosomal dominant 78

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Kilquist syndrome

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• schizophrenia

  Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001046.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A2	NM_001046.3	MANE Select	c.756+13396A>G		intron	N/A	NP_001037.1
	SLC12A2	NM_001256461.2		c.756+13396A>G		intron	N/A	NP_001243390.1
	SLC12A2	NR_046207.2		n.945+13396A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A2	ENST00000262461.7	TSL:1 MANE Select	c.756+13396A>G		intron	N/A	ENSP00000262461.2
	SLC12A2	ENST00000343225.4	TSL:1	c.756+13396A>G		intron	N/A	ENSP00000340878.4
	SLC12A2	ENST00000509205.5	TSL:1	n.756+13396A>G		intron	N/A	ENSP00000427109.1

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

African (AFR) AF: 0.954 AC: 39638 AN: 41554

American (AMR) AF: 0.818 AC: 12495 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.725 AC: 2512 AN: 3466

East Asian (EAS) AF: 0.625 AC: 3227 AN: 5166

South Asian (SAS) AF: 0.695 AC: 3345 AN: 4814

European-Finnish (FIN) AF: 0.866 AC: 9144 AN: 10560

Middle Eastern (MID) AF: 0.799 AC: 235 AN: 294

European-Non Finnish (NFE) AF: 0.770 AC: 52303 AN: 67896

Other (OTH) AF: 0.791 AC: 1668 AN: 2110

Alfa AF: 0.783 Hom.: 24288

Bravo AF: 0.828

Asia WGS AF: 0.697 AC: 2421 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.5
DANN	Benign	0.46
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1112956; hg19: chr5-127433798;