Variant 2-108002084-G-A 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+44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.355 in 1,573,448 control chromosomes in the GnomAD database, including 102,487 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.42 ( 14206 hom., cov: 32)

Exomes 𝑓: 0.35 ( 88281 hom. )

Consequence

SLC5A7
NM_021815.5 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.707

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=-0.89).

BP6

Variant 2-108002084-G-A is Benign according to our data. Variant chr2-108002084-G-A is described in ClinVar as [Benign]. Clinvar id is 1242137.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.563 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+44G>A		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+44G>A		intron_variant		1	NM_021815.5	ENSP00000264047.2		Q9GZV3
SLC5A7	ENST00000409059.5 linkuse as main transcript	c.741+44G>A		intron_variant		1		ENSP00000387346.1		Q9GZV3

Frequencies

GnomAD3 genomes

AF:

0.420

AC:

63900

AN:

151974

Hom.:

14171

Cov.:

show subpopulations

Gnomad AFR

AF:

0.569

Gnomad AMI

AF:

0.514

Gnomad AMR

AF:

0.459

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.253

Gnomad SAS

AF:

0.240

Gnomad FIN

AF:

0.457

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.346

Gnomad OTH

AF:

0.421

GnomAD3 exomes

AF:

0.366

AC:

85436

AN:

233320

Hom.:

16585

AF XY:

0.355

AC XY:

44764

AN XY:

126042

show subpopulations

Gnomad AFR exome

AF:

0.575

Gnomad AMR exome

AF:

0.475

Gnomad ASJ exome

AF:

0.311

Gnomad EAS exome

AF:

0.238

Gnomad SAS exome

AF:

0.247

Gnomad FIN exome

AF:

0.447

Gnomad NFE exome

AF:

0.344

Gnomad OTH exome

AF:

0.366

GnomAD4 exome

AF:

0.347

AC:

493887

AN:

1421356

Hom.:

88281

Cov.:

AF XY:

0.344

AC XY:

241439

AN XY:

702068

show subpopulations

Gnomad4 AFR exome

AF:

0.581

Gnomad4 AMR exome

AF:

0.469

Gnomad4 ASJ exome

AF:

0.308

Gnomad4 EAS exome

AF:

0.279

Gnomad4 SAS exome

AF:

0.248

Gnomad4 FIN exome

AF:

0.435

Gnomad4 NFE exome

AF:

0.343

Gnomad4 OTH exome

AF:

0.347

GnomAD4 genome

AF:

0.421

AC:

63973

AN:

152092

Hom.:

14206

Cov.:

AF XY:

0.424

AC XY:

31523

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.569

Gnomad4 AMR

AF:

0.459

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.253

Gnomad4 SAS

AF:

0.238

Gnomad4 FIN

AF:

0.457

Gnomad4 NFE

AF:

0.346

Gnomad4 OTH

AF:

0.416

Alfa

AF:

0.350

Hom.:

13482

Bravo

AF:

0.429

Asia WGS

AF:

0.279

AC:

971

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	Jul 06, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital myasthenic syndrome 20

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Neuronopathy, distal hereditary motor, type 7A

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.15

DANN

Benign

0.61

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