chr5-128165543-A-G

Variant names:

• chr5-128165543-A-G
• rs790154
• NM_001046.3:c.2617-2218A>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.2617-2218A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.828 in 152,162 control chromosomes in the GnomAD database, including 52,885 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 0.83 (52885 hom., cov: 31)
• Consequence: SLC12A2 NM_001046.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.420
• Publications: 9 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: PanelApp Australia, 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: PanelApp Australia, 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=-1.02).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.942 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A2	NM_001046.3	MANE Select	c.2617-2218A>G		intron	N/A	NP_001037.1	Q53ZR1
	SLC12A2	NM_001256461.2		c.2617-2218A>G		intron	N/A	NP_001243390.1	P55011-3
	SLC12A2	NR_046207.2		n.2806-2218A>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A2	ENST00000262461.7	TSL:1 MANE Select	c.2617-2218A>G		intron	N/A	ENSP00000262461.2	P55011-1
	SLC12A2	ENST00000343225.4	TSL:1	c.2617-2218A>G		intron	N/A	ENSP00000340878.4	P55011-3
	SLC12A2	ENST00000504416.5	TSL:1	n.319-2218A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.828 AC: 125895 AN: 152044 Hom.: 52824 Cov.: 31

Gnomad AFR AF: 0.950

Gnomad AMI AF: 0.896

Gnomad AMR AF: 0.819

Gnomad ASJ AF: 0.726

Gnomad EAS AF: 0.591

Gnomad SAS AF: 0.695

Gnomad FIN AF: 0.908

Gnomad MID AF: 0.815

Gnomad NFE AF: 0.776

Gnomad OTH AF: 0.795

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

GnomAD4 genome AF: 0.828 AC: 126010 AN: 152162 Hom.: 52885 Cov.: 31 AF XY: 0.831 AC XY: 61782 AN XY: 74390

African (AFR) AF: 0.950 AC: 39469 AN: 41554

American (AMR) AF: 0.820 AC: 12519 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 2516 AN: 3466

East Asian (EAS) AF: 0.591 AC: 3050 AN: 5162

South Asian (SAS) AF: 0.697 AC: 3350 AN: 4806

European-Finnish (FIN) AF: 0.908 AC: 9624 AN: 10604

Middle Eastern (MID) AF: 0.812 AC: 237 AN: 292

European-Non Finnish (NFE) AF: 0.776 AC: 52754 AN: 67982

Other (OTH) AF: 0.793 AC: 1674 AN: 2110

Alfa AF: 0.785 Hom.: 23639

Bravo AF: 0.829

Asia WGS AF: 0.684 AC: 2374 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.64
PhyloP100		0.42
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: rs790154; hg19: chr5-127501235;