Genetic Variant ENST00000395750.6:c.5+229C>T (chr11-35419707-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000395750.6(SLC1A2):c.5+229C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00731 in 173,038 control chromosomes in the GnomAD database, including 6 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 0.0075 ( 6 hom., cov: 31)

Exomes 𝑓: 0.0057 ( 0 hom. )

Consequence

SLC1A2
ENST00000395750.6 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.637

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 links:

SLC1A2-AS2 (HGNC:40535): (SLC1A2 antisense RNA 2)

SLC1A2-AS2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.59).

BS2

High Homozygotes in GnomAd4 at 6 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000395750.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A2	NM_001439342.1	c.5+229C>T	intron	N/A	NP_001426271.1
SLC1A2	NM_001195728.3	c.-130+229C>T	intron	N/A	NP_001182657.1	P43004-2
SLC1A2	NM_001252652.2	c.-167+201C>T	intron	N/A	NP_001239581.1	P43004-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A2	ENST00000395750.6	TSL:1	c.5+229C>T	intron	N/A	ENSP00000379099.2	A0A2U3TZS7
SLC1A2	ENST00000901505.1		c.-42+229C>T	intron	N/A	ENSP00000571564.1
SLC1A2	ENST00000395753.6	TSL:2	c.-11+201C>T	intron	N/A	ENSP00000379102.1	P43004-2

Frequencies

GnomAD3 genomes

AF:

0.00755

AC:

1148

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00159

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00943

Gnomad ASJ

AF:

0.00981

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00269

Gnomad FIN

AF:

0.00320

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.0121

Gnomad OTH

AF:

0.0129

GnomAD4 exome

AF:

0.00566

AC:

118

AN:

20844

Hom.:

Cov.:

AF XY:

0.00596

AC XY:

AN XY:

11578

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

146

American (AMR)

AF:

0.00694

AC:

AN:

288

Ashkenazi Jewish (ASJ)

AF:

0.0240

AC:

AN:

292

East Asian (EAS)

AF:

0.00

AC:

AN:

132

South Asian (SAS)

AF:

0.00408

AC:

AN:

3186

European-Finnish (FIN)

AF:

0.00149

AC:

AN:

8746

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0103

AC:

AN:

7398

Other (OTH)

AF:

0.0117

AC:

AN:

600

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.512

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00754

AC:

1147

AN:

152194

Hom.:

Cov.:

AF XY:

0.00708

AC XY:

527

AN XY:

74416

show subpopulations

African (AFR)

AF:

0.00159

AC:

AN:

41536

American (AMR)

AF:

0.00941

AC:

144

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.00981

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5154

South Asian (SAS)

AF:

0.00270

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00320

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0121

AC:

826

AN:

67992

Other (OTH)

AF:

0.0128

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

110

165

220

275

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.0117

Hom.:

Bravo

AF:

0.00846

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.59

CADD

Benign

(source)

DANN

Benign

0.94

PhyloP100

0.64

PromoterAI

-0.011

Neutral

(source)

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over