11-35411901-A-G

Variant names:

• chr11-35411901-A-G
• rs1923291
• NM_004171.4:c.17+7049T>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+7049T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.689 in 152,018 control chromosomes in the GnomAD database, including 36,673 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 0.69 (36673 hom., cov: 32)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.323
• 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: 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4	c.17+7049T>C		intron_variant	Intron 1 of 10	ENST00000278379.9	NP_004162.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9	c.17+7049T>C		intron_variant	Intron 1 of 10	1	NM_004171.4	ENSP00000278379.3

Frequencies

GnomAD3 genomes AF: 0.689 AC: 104671 AN: 151900 Hom.: 36624 Cov.: 32

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.493

Gnomad AMR AF: 0.679

Gnomad ASJ AF: 0.767

Gnomad EAS AF: 0.779

Gnomad SAS AF: 0.684

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.744

Gnomad NFE AF: 0.612

Gnomad OTH AF: 0.662

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

GnomAD4 genome AF: 0.689 AC: 104777 AN: 152018 Hom.: 36673 Cov.: 32 AF XY: 0.694 AC XY: 51585 AN XY: 74304

African (AFR) AF: 0.806 AC: 33432 AN: 41486

American (AMR) AF: 0.680 AC: 10389 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.767 AC: 2663 AN: 3470

East Asian (EAS) AF: 0.779 AC: 4033 AN: 5180

South Asian (SAS) AF: 0.684 AC: 3292 AN: 4812

European-Finnish (FIN) AF: 0.697 AC: 7328 AN: 10516

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.612 AC: 41570 AN: 67956

Other (OTH) AF: 0.665 AC: 1401 AN: 2108

Alfa AF: 0.637 Hom.: 14648

Bravo AF: 0.694

Asia WGS AF: 0.700 AC: 2425 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.2
DANN	Benign	0.74
PhyloP100		0.32
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: rs1923291; hg19: chr11-35433448;