Variant 9-4561426-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004170.6(SLC1A1):c.233-23T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0153 in 1,420,344 control chromosomes in the GnomAD database, including 1,086 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.051 ( 552 hom., cov: 32)

Exomes 𝑓: 0.011 ( 534 hom. )

Consequence

SLC1A1
NM_004170.6 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.72

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:

SPATA6L (HGNC:25472): (spermatogenesis associated 6 like) Predicted to enable myosin light chain binding activity. Predicted to be involved in spermatogenesis. Predicted to be located in sperm connecting piece. [provided by Alliance of Genome Resources, Apr 2022]

SPATA6L links:

SLC1A1 (HGNC:):

SLC1A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BP6

Variant 9-4561426-T-C is Benign according to our data. Variant chr9-4561426-T-C is described in ClinVar as [Benign]. Clinvar id is 1259249.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.16 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A1	NM_004170.6 linkuse as main transcript	c.233-23T>C		intron_variant		ENST00000262352.8	NP_004161.4	P43005

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
SLC1A1	ENST00000262352.8 linkuse as main transcript	c.233-23T>C	intron_variant	1	NM_004170.6	ENSP00000262352.3	P43005
SPATA6L	ENST00000485616.5 linkuse as main transcript	n.*782-7038A>G	intron_variant	2		ENSP00000420003.1	D3DRI0
SLC1A1	ENST00000490167.1 linkuse as main transcript	n.277-23T>C	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.0508

AC:

7734

AN:

152132

Hom.:

552

Cov.:

show subpopulations

Gnomad AFR

AF:

0.163

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0198

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00186

Gnomad FIN

AF:

0.00885

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00742

Gnomad OTH

AF:

0.0325

GnomAD3 exomes

AF:

0.0166

AC:

4174

AN:

251304

Hom.:

237

AF XY:

0.0135

AC XY:

1834

AN XY:

135808

show subpopulations

Gnomad AFR exome

AF:

0.171

Gnomad AMR exome

AF:

0.00827

Gnomad ASJ exome

AF:

0.000695

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00180

Gnomad FIN exome

AF:

0.00921

Gnomad NFE exome

AF:

0.00680

Gnomad OTH exome

AF:

0.0124

GnomAD4 exome

AF:

0.0110

AC:

13991

AN:

1268094

Hom.:

534

Cov.:

AF XY:

0.0100

AC XY:

6439

AN XY:

641506

show subpopulations

Gnomad4 AFR exome

AF:

0.173

Gnomad4 AMR exome

AF:

0.00987

Gnomad4 ASJ exome

AF:

0.000440

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00180

Gnomad4 FIN exome

AF:

0.00905

Gnomad4 NFE exome

AF:

0.00745

Gnomad4 OTH exome

AF:

0.0141

GnomAD4 genome

AF:

0.0509

AC:

7749

AN:

152250

Hom.:

552

Cov.:

AF XY:

0.0496

AC XY:

3691

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.163

Gnomad4 AMR

AF:

0.0198

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00207

Gnomad4 FIN

AF:

0.00885

Gnomad4 NFE

AF:

0.00742

Gnomad4 OTH

AF:

0.0321

Alfa

AF:

0.0158

Hom.:

108

Bravo

AF:

0.0565

Asia WGS

AF:

0.00953

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 16, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

DANN

Benign

0.47

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