rs186987

Variant names:

• chr15-34327148-T-C
• rs186987
• NM_001365088.1:c.271+9262A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001365088.1(SLC12A6):​c.271+9262A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.259 in 151,862 control chromosomes in the GnomAD database, including 7,268 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 0.26 (7268 hom., cov: 31)
• Consequence: SLC12A6 NM_001365088.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0850
• Publications: 3 publications found

Genes affected

SLC12A6 (HGNC:10914): (solute carrier family 12 member 6) This gene is a member of the K-Cl cotransporter (KCC) family. K-Cl cotransporters are integral membrane proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The proteins encoded by this gene are activated by cell swelling induced by hypotonic conditions. Alternate splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are associated with agenesis of the corpus callosum with peripheral neuropathy. [provided by RefSeq, Jul 2008]

SLC12A6 Gene-Disease associations (from GenCC):

• agenesis of the corpus callosum with peripheral neuropathy

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae), Orphanet
• Charcot-Marie-Tooth disease, axonal, IIa 2II

  Inheritance: AD Classification: STRONG 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.518 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC12A6	NM_001365088.1	c.271+9262A>G		intron_variant	Intron 2 of 25	ENST00000354181.8	NP_001352017.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC12A6	ENST00000354181.8	c.271+9262A>G		intron_variant	Intron 2 of 25	1	NM_001365088.1	ENSP00000346112.3

Frequencies

GnomAD3 genomes AF: 0.259 AC: 39286 AN: 151744 Hom.: 7264 Cov.: 31

Gnomad AFR AF: 0.524

Gnomad AMI AF: 0.214

Gnomad AMR AF: 0.197

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.0863

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.144

Gnomad OTH AF: 0.242

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

GnomAD4 genome AF: 0.259 AC: 39323 AN: 151862 Hom.: 7268 Cov.: 31 AF XY: 0.255 AC XY: 18916 AN XY: 74236

African (AFR) AF: 0.524 AC: 21633 AN: 41318

American (AMR) AF: 0.197 AC: 3001 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.149 AC: 517 AN: 3470

East Asian (EAS) AF: 0.328 AC: 1689 AN: 5152

South Asian (SAS) AF: 0.208 AC: 1000 AN: 4808

European-Finnish (FIN) AF: 0.0863 AC: 912 AN: 10568

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.144 AC: 9789 AN: 67972

Other (OTH) AF: 0.241 AC: 508 AN: 2108

Alfa AF: 0.204 Hom.: 583

Bravo AF: 0.280

Asia WGS AF: 0.248 AC: 862 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		0.085
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs186987; hg19: chr15-34619349;