Genetic Variant NM_004171.4:c.-463A>C (chr11-35419429-T-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_004171.4(SLC1A2):c.-463A>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.526 in 181,614 control chromosomes in the GnomAD database, including 27,522 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 0.54 ( 24311 hom., cov: 34)

Exomes 𝑓: 0.45 ( 3211 hom. )

Consequence

SLC1A2
NM_004171.4 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.719

Publications

33 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.766 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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
SLC1A2	NM_004171.4	MANE Select	c.-463A>C	5_prime_UTR	Exon 1 of 11	NP_004162.2
SLC1A2	NM_001439343.1		c.-463A>C	5_prime_UTR	Exon 1 of 10	NP_001426272.1
SLC1A2	NM_001439342.1		c.5+507A>C	intron	N/A	NP_001426271.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC1A2	ENST00000278379.9	TSL:1 MANE Select	c.-463A>C	5_prime_UTR	Exon 1 of 11	ENSP00000278379.3	P43004-1
SLC1A2	ENST00000395750.6	TSL:1	c.5+507A>C	intron	N/A	ENSP00000379099.2	A0A2U3TZS7
SLC1A2	ENST00000644779.1		c.-698A>C	5_prime_UTR	Exon 1 of 14	ENSP00000494258.1	A0A2R8YD46

Frequencies

GnomAD3 genomes

AF:

0.540

AC:

82058

AN:

151948

Hom.:

24261

Cov.:

show subpopulations

Gnomad AFR

AF:

0.773

Gnomad AMI

AF:

0.360

Gnomad AMR

AF:

0.587

Gnomad ASJ

AF:

0.524

Gnomad EAS

AF:

0.718

Gnomad SAS

AF:

0.464

Gnomad FIN

AF:

0.391

Gnomad MID

AF:

0.532

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.514

GnomAD4 exome

AF:

0.452

AC:

13355

AN:

29556

Hom.:

3211

Cov.:

AF XY:

0.446

AC XY:

6809

AN XY:

15252

show subpopulations

African (AFR)

AF:

0.773

AC:

758

AN:

980

American (AMR)

AF:

0.626

AC:

383

AN:

612

Ashkenazi Jewish (ASJ)

AF:

0.492

AC:

548

AN:

1114

East Asian (EAS)

AF:

0.767

AC:

1677

AN:

2186

South Asian (SAS)

AF:

0.445

AC:

194

AN:

436

European-Finnish (FIN)

AF:

0.395

AC:

978

AN:

2474

Middle Eastern (MID)

AF:

0.576

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.396

AC:

7813

AN:

19724

Other (OTH)

AF:

0.488

AC:

921

AN:

1886

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

353

705

1058

1410

1763

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

156

208

260

<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:

0.540

AC:

82165

AN:

152058

Hom.:

24311

Cov.:

AF XY:

0.540

AC XY:

40170

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.773

AC:

32098

AN:

41534

American (AMR)

AF:

0.588

AC:

8988

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.524

AC:

1818

AN:

3470

East Asian (EAS)

AF:

0.717

AC:

3683

AN:

5134

South Asian (SAS)

AF:

0.464

AC:

2238

AN:

4820

European-Finnish (FIN)

AF:

0.391

AC:

4142

AN:

10590

Middle Eastern (MID)

AF:

0.541

AC:

158

AN:

292

European-Non Finnish (NFE)

AF:

0.407

AC:

27633

AN:

67904

Other (OTH)

AF:

0.511

AC:

1079

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

1825

3651

5476

7302

9127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

682

1364

2046

2728

3410

<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:

0.469

Hom.:

2767

Bravo

AF:

0.568

Asia WGS

AF:

0.581

AC:

2017

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.73

PhyloP100

-0.72

PromoterAI

0.13

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(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