rs5791053

Variant names:

• chr11-35371110-G-GT
• rs5791053
• NM_004171.4:c.17+47839_17+47840insA

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_004171.4(SLC1A2):​c.17+47839_17+47840insA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.45 (16417 hom., cov: 0)
  • Exomes 𝑓: 0.49 (102830 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.15
• Publications: 1 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: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Ambry Genetics
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.71 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	NM_004171.4	MANE Select	c.17+47839_17+47840insA		intron	N/A	NP_004162.2
	SLC1A2	NM_001439342.1		c.5+48825_5+48826insA		intron	N/A	NP_001426271.1
	SLC1A2	NM_001195728.3		c.-129-48432_-129-48431insA		intron	N/A	NP_001182657.1	P43004-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.17+47839_17+47840insA		intron	N/A	ENSP00000278379.3	P43004-1
	SLC1A2	ENST00000395750.6	TSL:1	c.5+48825_5+48826insA		intron	N/A	ENSP00000379099.2	A0A2U3TZS7
	SLC1A2	ENST00000644779.1		c.-536-47802_-536-47801insA		intron	N/A	ENSP00000494258.1	A0A2R8YD46

Frequencies

GnomAD3 genomes AF: 0.448 AC: 67917 AN: 151710 Hom.: 16406 Cov.: 0

Gnomad AFR AF: 0.276

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.568

Gnomad ASJ AF: 0.566

Gnomad EAS AF: 0.729

Gnomad SAS AF: 0.645

Gnomad FIN AF: 0.442

Gnomad MID AF: 0.510

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.472

GnomAD4 exome AF: 0.495 AC: 409988 AN: 828334 Hom.: 102830 Cov.: 2 AF XY: 0.496 AC XY: 189632 AN XY: 382652

African (AFR) AF: 0.251 AC: 3946 AN: 15704

American (AMR) AF: 0.569 AC: 556 AN: 978

Ashkenazi Jewish (ASJ) AF: 0.593 AC: 3029 AN: 5110

East Asian (EAS) AF: 0.742 AC: 2674 AN: 3606

South Asian (SAS) AF: 0.642 AC: 10503 AN: 16368

European-Finnish (FIN) AF: 0.427 AC: 117 AN: 274

Middle Eastern (MID) AF: 0.571 AC: 922 AN: 1616

European-Non Finnish (NFE) AF: 0.494 AC: 374395 AN: 757528

Other (OTH) AF: 0.510 AC: 13846 AN: 27150

GnomAD4 genome AF: 0.448 AC: 67954 AN: 151828 Hom.: 16417 Cov.: 0 AF XY: 0.456 AC XY: 33872 AN XY: 74222

African (AFR) AF: 0.275 AC: 11410 AN: 41416

American (AMR) AF: 0.568 AC: 8676 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.566 AC: 1961 AN: 3466

East Asian (EAS) AF: 0.730 AC: 3752 AN: 5140

South Asian (SAS) AF: 0.646 AC: 3107 AN: 4808

European-Finnish (FIN) AF: 0.442 AC: 4660 AN: 10548

Middle Eastern (MID) AF: 0.524 AC: 152 AN: 290

European-Non Finnish (NFE) AF: 0.485 AC: 32915 AN: 67874

Other (OTH) AF: 0.474 AC: 1001 AN: 2110

Alfa AF: 0.459 Hom.: 2011

Bravo AF: 0.449

Asia WGS AF: 0.620 AC: 2156 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.2
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs5791053;

hg19: chr11-35392657;