Variant 2-108002058-C-T 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_021815.5(SLC5A7):c.741+18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,595,768 control chromosomes in the GnomAD database, including 10,120 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1471 hom., cov: 32)

Exomes 𝑓: 0.10 ( 8649 hom. )

Consequence

SLC5A7
NM_021815.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -0.325

Variant links:

Genes affected

SLC5A7 (HGNC:14025): (solute carrier family 5 member 7) This gene encodes a sodium ion- and chloride ion-dependent high-affinity transporter that mediates choline uptake for acetylcholine synthesis in cholinergic neurons. The protein transports choline from the extracellular space into presynaptic terminals for synthesis into acetylcholine. Increased choline uptake results from increased density of this protein in synaptosomal plasma membranes in response to depolarization of cholinergic terminals. Dysfunction of cholinergic signaling has been implicated in various disorders including depression, attention-deficit disorder, and schizophrenia. An allelic variant of this gene is associated with autosomal dominant distal hereditary motor neuronopathy type VIIA. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jul 2015]

SLC5A7 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-108002058-C-T is Benign according to our data. Variant chr2-108002058-C-T is described in ClinVar as [Benign]. Clinvar id is 261429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-108002058-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A7	NM_021815.5 linkuse as main transcript	c.741+18C>T		intron_variant		ENST00000264047.3	NP_068587.1	Q9GZV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A7	ENST00000264047.3 linkuse as main transcript	c.741+18C>T		intron_variant		1	NM_021815.5	ENSP00000264047.2		Q9GZV3
SLC5A7	ENST00000409059.5 linkuse as main transcript	c.741+18C>T		intron_variant		1		ENSP00000387346.1		Q9GZV3

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19724

AN:

152080

Hom.:

1464

Cov.:

show subpopulations

Gnomad AFR

AF:

0.173

Gnomad AMI

AF:

0.242

Gnomad AMR

AF:

0.187

Gnomad ASJ

AF:

0.0524

Gnomad EAS

AF:

0.145

Gnomad SAS

AF:

0.0389

Gnomad FIN

AF:

0.137

Gnomad MID

AF:

0.0538

Gnomad NFE

AF:

0.0977

Gnomad OTH

AF:

0.117

GnomAD3 exomes

AF:

0.123

AC:

29596

AN:

241268

Hom.:

2309

AF XY:

0.113

AC XY:

14678

AN XY:

130148

show subpopulations

Gnomad AFR exome

AF:

0.177

Gnomad AMR exome

AF:

0.251

Gnomad ASJ exome

AF:

0.0591

Gnomad EAS exome

AF:

0.155

Gnomad SAS exome

AF:

0.0345

Gnomad FIN exome

AF:

0.139

Gnomad NFE exome

AF:

0.0974

Gnomad OTH exome

AF:

0.105

GnomAD4 exome

AF:

0.104

AC:

150273

AN:

1443570

Hom.:

8649

Cov.:

AF XY:

0.101

AC XY:

72435

AN XY:

715574

show subpopulations

Gnomad4 AFR exome

AF:

0.177

Gnomad4 AMR exome

AF:

0.243

Gnomad4 ASJ exome

AF:

0.0544

Gnomad4 EAS exome

AF:

0.135

Gnomad4 SAS exome

AF:

0.0338

Gnomad4 FIN exome

AF:

0.130

Gnomad4 NFE exome

AF:

0.101

Gnomad4 OTH exome

AF:

0.0992

GnomAD4 genome

AF:

0.130

AC:

19765

AN:

152198

Hom.:

1471

Cov.:

AF XY:

0.130

AC XY:

9685

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.174

Gnomad4 AMR

AF:

0.187

Gnomad4 ASJ

AF:

0.0524

Gnomad4 EAS

AF:

0.145

Gnomad4 SAS

AF:

0.0385

Gnomad4 FIN

AF:

0.137

Gnomad4 NFE

AF:

0.0977

Gnomad4 OTH

AF:

0.115

Alfa

AF:

0.117

Hom.:

326

Bravo

AF:

0.139

Asia WGS

AF:

0.100

AC:

346

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 11, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Neuronopathy, distal hereditary motor, type 7A;C4310694:Congenital myasthenic syndrome 20

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

5.2

DANN

Benign

0.51

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