NM_004171.4:c.17+49089T>C

Variant names:

• chr11-35369861-A-G
• rs4756224
• NM_004171.4:c.17+49089T>C

Variant summary

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

The NM_004171.4(SLC1A2):​c.17+49089T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,064 control chromosomes in the GnomAD database, including 6,199 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 0.28 (6199 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.84
• Publications: 2 publications found

Genes affected

SLC1A2 (HGNC:10940): (solute carrier family 1 member 2) This gene encodes a member of a family of solute transporter proteins. The membrane-bound protein is the principal transporter that clears the excitatory neurotransmitter glutamate from the extracellular space at synapses in the central nervous system. Glutamate clearance is necessary for proper synaptic activation and to prevent neuronal damage from excessive activation of glutamate receptors. Improper regulation of this gene is thought to be associated with several neurological disorders. Alternatively spliced transcript variants of this gene have been identified. [provided by RefSeq, Jun 2017]

SLC1A2 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 41

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, MODERATE, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.329 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004171.4. 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
	SLC1A2	NM_004171.4	MANE Select	c.17+49089T>C		intron	N/A	NP_004162.2
	SLC1A2	NM_001439342.1		c.5+50075T>C		intron	N/A	NP_001426271.1
	SLC1A2	NM_001195728.3		c.-129-47182T>C		intron	N/A	NP_001182657.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.17+49089T>C		intron	N/A	ENSP00000278379.3
	SLC1A2	ENST00000395750.6	TSL:1	c.5+50075T>C		intron	N/A	ENSP00000379099.2
	SLC1A2	ENST00000644779.1		c.-536-46552T>C		intron	N/A	ENSP00000494258.1

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42899 AN: 151946 Hom.: 6190 Cov.: 32

Gnomad AFR AF: 0.333

Gnomad AMI AF: 0.412

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.260

Gnomad OTH AF: 0.264

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

GnomAD4 genome AF: 0.282 AC: 42931 AN: 152064 Hom.: 6199 Cov.: 32 AF XY: 0.280 AC XY: 20835 AN XY: 74324

African (AFR) AF: 0.333 AC: 13826 AN: 41460

American (AMR) AF: 0.246 AC: 3764 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 975 AN: 3470

East Asian (EAS) AF: 0.221 AC: 1141 AN: 5166

South Asian (SAS) AF: 0.264 AC: 1274 AN: 4830

European-Finnish (FIN) AF: 0.310 AC: 3275 AN: 10564

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.260 AC: 17656 AN: 67972

Other (OTH) AF: 0.265 AC: 559 AN: 2108

Alfa AF: 0.141 Hom.: 237

Bravo AF: 0.281

Asia WGS AF: 0.261 AC: 905 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.043
DANN	Benign	0.63
PhyloP100		-1.8
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: rs4756224; hg19: chr11-35391408;