Genetic Variant NM_004171.4:c.17+47839_17+47840insA (chr11-35371110-G-GT) – ACMG Classification: Benign (-8 pts)

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

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.15

Publications

1 publications found

Variant links:

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

SLC1A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A2	NM_004171.4 link	c.17+47839_17+47840insA		intron_variant	Intron 1 of 10	ENST00000278379.9	NP_004162.2	P43004-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A2	ENST00000278379.9 link	c.17+47839_17+47840insA		intron_variant	Intron 1 of 10	1	NM_004171.4	ENSP00000278379.3		P43004-1

Frequencies

GnomAD3 genomes

AF:

0.448

AC:

67917

AN:

151710

Hom.:

16406

Cov.:

show subpopulations

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.:

AF XY:

0.496

AC XY:

189632

AN XY:

382652

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.465

Heterozygous variant carriers

8182

16364

24545

32727

40909

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15006

30012

45018

60024

75030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.448

AC:

67954

AN:

151828

Hom.:

16417

Cov.:

AF XY:

0.456

AC XY:

33872

AN XY:

74222

show subpopulations

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

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1782

3564

5346

7128

8910

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

628

1256

1884

2512

3140

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

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 v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.2

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over