Variant 9-4490760-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_004170.6(SLC1A1):c.81G>C(p.Ala27=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0232 in 1,611,722 control chromosomes in the GnomAD database, including 534 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.016 ( 35 hom., cov: 34)

Exomes 𝑓: 0.024 ( 499 hom. )

Consequence

SLC1A1
NM_004170.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.70

Variant links:

Genes affected

SLC1A1 (HGNC:10939): (solute carrier family 1 member 1) This gene encodes a member of the high-affinity glutamate transporters that play an essential role in transporting glutamate across plasma membranes. In brain, these transporters are crucial in terminating the postsynaptic action of the neurotransmitter glutamate, and in maintaining extracellular glutamate concentrations below neurotoxic levels. This transporter also transports aspartate, and mutations in this gene are thought to cause dicarboxylicamino aciduria, also known as glutamate-aspartate transport defect. [provided by RefSeq, Mar 2010]

SLC1A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 9-4490760-G-C is Benign according to our data. Variant chr9-4490760-G-C is described in ClinVar as [Benign]. Clinvar id is 367033.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.7 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0163 (2481/152290) while in subpopulation NFE AF= 0.0264 (1794/68002). AF 95% confidence interval is 0.0254. There are 35 homozygotes in gnomad4. There are 1128 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 35 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A1	NM_004170.6 linkuse as main transcript	c.81G>C	p.Ala27=	synonymous_variant	1/12	ENST00000262352.8	NP_004161.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A1	ENST00000262352.8 linkuse as main transcript	c.81G>C	p.Ala27=	synonymous_variant	1/12	1	NM_004170.6	ENSP00000262352	P1

Frequencies

GnomAD3 genomes

AF:

0.0163

AC:

2481

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00533

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00766

Gnomad ASJ

AF:

0.00720

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00559

Gnomad FIN

AF:

0.0256

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0264

Gnomad OTH

AF:

0.0105

GnomAD3 exomes

AF:

0.0157

AC:

3856

AN:

245466

Hom.:

AF XY:

0.0157

AC XY:

2097

AN XY:

133552

show subpopulations

Gnomad AFR exome

AF:

0.00439

Gnomad AMR exome

AF:

0.00666

Gnomad ASJ exome

AF:

0.00281

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00637

Gnomad FIN exome

AF:

0.0272

Gnomad NFE exome

AF:

0.0244

Gnomad OTH exome

AF:

0.0150

GnomAD4 exome

AF:

0.0239

AC:

34924

AN:

1459432

Hom.:

499

Cov.:

AF XY:

0.0233

AC XY:

16887

AN XY:

726128

show subpopulations

Gnomad4 AFR exome

AF:

0.00372

Gnomad4 AMR exome

AF:

0.00701

Gnomad4 ASJ exome

AF:

0.00392

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00669

Gnomad4 FIN exome

AF:

0.0255

Gnomad4 NFE exome

AF:

0.0281

Gnomad4 OTH exome

AF:

0.0200

GnomAD4 genome

AF:

0.0163

AC:

2481

AN:

152290

Hom.:

Cov.:

AF XY:

0.0151

AC XY:

1128

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.00532

Gnomad4 AMR

AF:

0.00765

Gnomad4 ASJ

AF:

0.00720

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00559

Gnomad4 FIN

AF:

0.0256

Gnomad4 NFE

AF:

0.0264

Gnomad4 OTH

AF:

0.0104

Alfa

AF:

0.0111

Hom.:

Bravo

AF:

0.0146

Asia WGS

AF:

0.00202

AC:

AN:

3474

EpiCase

AF:

0.0255

EpiControl

AF:

0.0231

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Dicarboxylic aminoaciduria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

9.1

DANN

Benign

0.93

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over