NM_020708.5:c.612+571G>T

Variant names:

• chr20-46037956-G-T
• rs3848726
• NM_020708.5:c.612+571G>T

Variant summary

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

The NM_020708.5(SLC12A5):​c.612+571G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.272 in 152,040 control chromosomes in the GnomAD database, including 6,857 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 0.27 (6857 hom., cov: 31)
• Consequence: SLC12A5 NM_020708.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.08
• Publications: 12 publications found

Genes affected

SLC12A5 (HGNC:13818): (solute carrier family 12 member 5) K-Cl cotransporters are proteins that lower intracellular chloride concentrations below the electrochemical equilibrium potential. The protein encoded by this gene is an integral membrane K-Cl cotransporter that can function in either a net efflux or influx pathway, depending on the chemical concentration gradients of potassium and chloride. The encoded protein can act as a homomultimer, or as a heteromultimer with other K-Cl cotransporters, to maintain chloride homeostasis in neurons. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Sep 2008]

SLC12A5 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 34

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Illumina, Ambry Genetics
• epilepsy of infancy with migrating focal seizures

  Inheritance: AR Classification: STRONG Submitted by: G2P
• malignant migrating partial seizures of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• epilepsy, idiopathic generalized, susceptibility to, 14

  Inheritance: AD Classification: LIMITED, NO_KNOWN Submitted by: Illumina, Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020708.5. 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
	SLC12A5	NM_020708.5	MANE Select	c.612+571G>T		intron	N/A	NP_065759.1
	SLC12A5	NM_001134771.2		c.681+571G>T		intron	N/A	NP_001128243.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A5	ENST00000243964.7	TSL:1 MANE Select	c.612+571G>T		intron	N/A	ENSP00000243964.4
	SLC12A5	ENST00000616202.4	TSL:1	c.612+571G>T		intron	N/A	ENSP00000478369.1
	SLC12A5	ENST00000626937.2	TSL:1	c.509+674G>T		intron	N/A	ENSP00000485953.1

Frequencies

GnomAD3 genomes AF: 0.272 AC: 41366 AN: 151922 Hom.: 6863 Cov.: 31

Gnomad AFR AF: 0.0818

Gnomad AMI AF: 0.421

Gnomad AMR AF: 0.273

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.207

Gnomad SAS AF: 0.237

Gnomad FIN AF: 0.348

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.298

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

GnomAD4 genome AF: 0.272 AC: 41353 AN: 152040 Hom.: 6857 Cov.: 31 AF XY: 0.271 AC XY: 20155 AN XY: 74310

African (AFR) AF: 0.0815 AC: 3385 AN: 41524

American (AMR) AF: 0.273 AC: 4168 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1251 AN: 3470

East Asian (EAS) AF: 0.206 AC: 1065 AN: 5162

South Asian (SAS) AF: 0.239 AC: 1148 AN: 4810

European-Finnish (FIN) AF: 0.348 AC: 3677 AN: 10556

Middle Eastern (MID) AF: 0.344 AC: 99 AN: 288

European-Non Finnish (NFE) AF: 0.376 AC: 25555 AN: 67934

Other (OTH) AF: 0.295 AC: 622 AN: 2108

Alfa AF: 0.335 Hom.: 30544

Bravo AF: 0.257

Asia WGS AF: 0.194 AC: 678 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	8.1
DANN	Benign	0.75
PhyloP100		2.1
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: rs3848726; hg19: chr20-44666595;