rs2297201

Variant names:

• chr20-46056339-C-T
• rs2297201
• NM_020708.5:c.2911-26C>T

Your query was ambiguous. Multiple possible variants found:

• chr20-46056339-C-T
• chr20-46056339-C-A
• chr20-46056339-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_020708.5(SLC12A5):​c.2911-26C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0853 in 1,608,382 control chromosomes in the GnomAD database, including 9,206 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.098 (1050 hom., cov: 33)
  • Exomes 𝑓: 0.084 (8156 hom.)
• Consequence: SLC12A5 NM_020708.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.441
• Publications: 20 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: PanelApp Australia, 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, PanelApp Australia, Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 20-46056339-C-T is Benign according to our data. Variant chr20-46056339-C-T is described in ClinVar as Benign. ClinVar VariationId is 3255279.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.224 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A5	NM_020708.5	MANE Select	c.2911-26C>T		intron	N/A	NP_065759.1	Q9H2X9-2
	SLC12A5	NM_001134771.2		c.2980-26C>T		intron	N/A	NP_001128243.1	Q9H2X9-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC12A5	ENST00000243964.7	TSL:1 MANE Select	c.2911-26C>T		intron	N/A	ENSP00000243964.4	Q9H2X9-2
	SLC12A5	ENST00000616202.4	TSL:1	c.613-2142C>T		intron	N/A	ENSP00000478369.1	M4PM71
	SLC12A5	ENST00000626937.2	TSL:1	c.510-3260C>T		intron	N/A	ENSP00000485953.1	M4PNC0

Frequencies

GnomAD3 genomes AF: 0.0980 AC: 14901 AN: 152108 Hom.: 1040 Cov.: 33

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.0659

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.0340

Gnomad EAS AF: 0.235

Gnomad SAS AF: 0.148

Gnomad FIN AF: 0.0485

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0610

Gnomad OTH AF: 0.0992

GnomAD2 exomes AF: 0.128 AC: 31490 AN: 246302 AF XY: 0.118

Gnomad AFR exome AF: 0.123

Gnomad AMR exome AF: 0.360

Gnomad ASJ exome AF: 0.0337

Gnomad EAS exome AF: 0.223

Gnomad FIN exome AF: 0.0488

Gnomad NFE exome AF: 0.0616

Gnomad OTH exome AF: 0.0961

GnomAD4 exome AF: 0.0840 AC: 122265 AN: 1456156 Hom.: 8156 Cov.: 32 AF XY: 0.0844 AC XY: 61090 AN XY: 723756

African (AFR) AF: 0.119 AC: 3980 AN: 33334

American (AMR) AF: 0.342 AC: 15142 AN: 44320

Ashkenazi Jewish (ASJ) AF: 0.0353 AC: 905 AN: 25636

East Asian (EAS) AF: 0.256 AC: 10164 AN: 39628

South Asian (SAS) AF: 0.147 AC: 12557 AN: 85498

European-Finnish (FIN) AF: 0.0521 AC: 2773 AN: 53238

Middle Eastern (MID) AF: 0.0638 AC: 366 AN: 5734

European-Non Finnish (NFE) AF: 0.0644 AC: 71341 AN: 1108640

Other (OTH) AF: 0.0838 AC: 5037 AN: 60128

GnomAD4 genome AF: 0.0981 AC: 14927 AN: 152226 Hom.: 1050 Cov.: 33 AF XY: 0.100 AC XY: 7465 AN XY: 74422

African (AFR) AF: 0.117 AC: 4860 AN: 41536

American (AMR) AF: 0.200 AC: 3064 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0340 AC: 118 AN: 3470

East Asian (EAS) AF: 0.235 AC: 1217 AN: 5168

South Asian (SAS) AF: 0.147 AC: 710 AN: 4822

European-Finnish (FIN) AF: 0.0485 AC: 515 AN: 10612

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0611 AC: 4152 AN: 68008

Other (OTH) AF: 0.103 AC: 218 AN: 2108

Alfa AF: 0.0830 Hom.: 1434

Bravo AF: 0.115

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.8
DANN	Benign	0.53
PhyloP100		-0.44
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: rs2297201; hg19: chr20-44684978; COSMIC: COSV51643332; COSMIC: COSV51643332;