rs12682807

Positions:

Variant summary

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

The NM_004170.6(SLC1A1):c.875+8A>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,565,798 control chromosomes in the GnomAD database, including 10,104 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.086 ( 833 hom., cov: 32)

Exomes 𝑓: 0.11 ( 9271 hom. )

Consequence

SLC1A1
NM_004170.6 splice_region, intron

Scores

Splicing: ADA: 0.00002237

Clinical Significance

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

Conservation

PhyloP100: 0.832

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:

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=-0.78).

BP6

Variant 9-4574022-A-C is Benign according to our data. Variant chr9-4574022-A-C is described in ClinVar as [Benign]. Clinvar id is 367049.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC1A1	NM_004170.6 linkuse as main transcript	c.875+8A>C		splice_region_variant, intron_variant		ENST00000262352.8

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris
SLC1A1	ENST00000262352.8 linkuse as main transcript	c.875+8A>C	splice_region_variant, intron_variant	1	NM_004170.6	P1
SLC1A1	ENST00000422398.1 linkuse as main transcript	c.162+8A>C	splice_region_variant, intron_variant	4
SPATA6L	ENST00000485616.5 linkuse as main transcript	c.*782-19634T>G	intron_variant, NMD_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0862

AC:

13122

AN:

152164

Hom.:

832

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0210

Gnomad AMI

AF:

0.133

Gnomad AMR

AF:

0.0859

Gnomad ASJ

AF:

0.0343

Gnomad EAS

AF:

0.245

Gnomad SAS

AF:

0.0707

Gnomad FIN

AF:

0.147

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.108

Gnomad OTH

AF:

0.0793

GnomAD3 exomes

AF:

0.106

AC:

26578

AN:

251340

Hom.:

1819

AF XY:

0.102

AC XY:

13909

AN XY:

135832

show subpopulations

Gnomad AFR exome

AF:

0.0194

Gnomad AMR exome

AF:

0.106

Gnomad ASJ exome

AF:

0.0348

Gnomad EAS exome

AF:

0.250

Gnomad SAS exome

AF:

0.0641

Gnomad FIN exome

AF:

0.144

Gnomad NFE exome

AF:

0.105

Gnomad OTH exome

AF:

0.0951

GnomAD4 exome

AF:

0.109

AC:

154736

AN:

1413516

Hom.:

9271

Cov.:

AF XY:

0.107

AC XY:

75779

AN XY:

706132

show subpopulations

Gnomad4 AFR exome

AF:

0.0168

Gnomad4 AMR exome

AF:

0.103

Gnomad4 ASJ exome

AF:

0.0363

Gnomad4 EAS exome

AF:

0.193

Gnomad4 SAS exome

AF:

0.0641

Gnomad4 FIN exome

AF:

0.145

Gnomad4 NFE exome

AF:

0.114

Gnomad4 OTH exome

AF:

0.0993

GnomAD4 genome

AF:

0.0862

AC:

13121

AN:

152282

Hom.:

833

Cov.:

AF XY:

0.0879

AC XY:

6546

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0210

Gnomad4 AMR

AF:

0.0860

Gnomad4 ASJ

AF:

0.0343

Gnomad4 EAS

AF:

0.245

Gnomad4 SAS

AF:

0.0706

Gnomad4 FIN

AF:

0.147

Gnomad4 NFE

AF:

0.108

Gnomad4 OTH

AF:

0.0790

Alfa

AF:

0.0857

Hom.:

612

Bravo

AF:

0.0808

Asia WGS

AF:

0.142

AC:

494

AN:

3478

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

clinical testing

GeneDx

May 16, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.9

DANN

Benign

0.72

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000022

dbscSNV1_RF

Benign

0.0

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