rs1885345

Variant names:

• chr11-35371054-A-G
• rs1885345
• NM_004171.4:c.17+47896T>C

Your query was ambiguous. Multiple possible variants found:

• chr11-35371054-A-G
• chr11-35371054-A-T

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+47896T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 984,178 control chromosomes in the GnomAD database, including 289,514 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 0.82 (51349 hom., cov: 31)
  • Exomes 𝑓: 0.76 (238165 hom.)
• Consequence: SLC1A2 NM_004171.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.09
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.928 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+47896T>C		intron	N/A	NP_004162.2
	SLC1A2	NM_001252652.2		c.-124T>C		5_prime_UTR	Exon 2 of 12	NP_001239581.1
	SLC1A2	NM_001439342.1		c.5+48882T>C		intron	N/A	NP_001426271.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.17+47896T>C		intron	N/A	ENSP00000278379.3
	SLC1A2	ENST00000395750.6	TSL:1	c.5+48882T>C		intron	N/A	ENSP00000379099.2
	SLC1A2	ENST00000645634.1		c.-124T>C		5_prime_UTR	Exon 2 of 12	ENSP00000493945.1

Frequencies

GnomAD3 genomes AF: 0.818 AC: 124280 AN: 151960 Hom.: 51307 Cov.: 31

Gnomad AFR AF: 0.913

Gnomad AMI AF: 0.765

Gnomad AMR AF: 0.844

Gnomad ASJ AF: 0.848

Gnomad EAS AF: 0.950

Gnomad SAS AF: 0.911

Gnomad FIN AF: 0.754

Gnomad MID AF: 0.845

Gnomad NFE AF: 0.747

Gnomad OTH AF: 0.799

GnomAD4 exome AF: 0.755 AC: 628485 AN: 832100 Hom.: 238165 Cov.: 25 AF XY: 0.755 AC XY: 289976 AN XY: 384288

African (AFR) AF: 0.927 AC: 14623 AN: 15774

American (AMR) AF: 0.842 AC: 829 AN: 984

Ashkenazi Jewish (ASJ) AF: 0.862 AC: 4435 AN: 5148

East Asian (EAS) AF: 0.956 AC: 3471 AN: 3630

South Asian (SAS) AF: 0.900 AC: 14803 AN: 16448

European-Finnish (FIN) AF: 0.777 AC: 216 AN: 278

Middle Eastern (MID) AF: 0.854 AC: 1384 AN: 1620

European-Non Finnish (NFE) AF: 0.746 AC: 567343 AN: 760948

Other (OTH) AF: 0.784 AC: 21381 AN: 27270

GnomAD4 genome AF: 0.818 AC: 124376 AN: 152078 Hom.: 51349 Cov.: 31 AF XY: 0.822 AC XY: 61074 AN XY: 74320

African (AFR) AF: 0.913 AC: 37880 AN: 41504

American (AMR) AF: 0.844 AC: 12910 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.848 AC: 2943 AN: 3470

East Asian (EAS) AF: 0.950 AC: 4906 AN: 5164

South Asian (SAS) AF: 0.911 AC: 4387 AN: 4818

European-Finnish (FIN) AF: 0.754 AC: 7955 AN: 10552

Middle Eastern (MID) AF: 0.844 AC: 248 AN: 294

European-Non Finnish (NFE) AF: 0.747 AC: 50758 AN: 67956

Other (OTH) AF: 0.802 AC: 1693 AN: 2112

Alfa AF: 0.781 Hom.: 88588

Bravo AF: 0.830

Asia WGS AF: 0.905 AC: 3144 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	1.5
DANN	Benign	0.62
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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: rs1885345; hg19: chr11-35392601;