2-108002084-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Publications

11 publications found

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 Gene-Disease associations (from GenCC):

neuronopathy, distal hereditary motor, type 7A
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)
congenital myasthenic syndrome 20
Inheritance: AR Classification: STRONG Submitted by: G2P, Ambry Genetics, PanelApp Australia, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
distal hereditary motor neuropathy type 7
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
presynaptic congenital myasthenic syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SLC5A7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SLC5A7	NM_021815.5 link	c.741+44G>A		intron_variant	Intron 6 of 8	ENST00000264047.3	NP_068587.1	Q9GZV3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A7	ENST00000264047.3 link	c.741+44G>A		intron_variant	Intron 6 of 8	1	NM_021815.5	ENSP00000264047.2		Q9GZV3
SLC5A7	ENST00000409059.5 link	c.741+44G>A		intron_variant	Intron 6 of 8	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

GnomAD2 exomes

AF:

0.366

AC:

85436

AN:

233320

AF XY:

0.355

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 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

African (AFR)

AF:

0.581

AC:

18508

AN:

31830

American (AMR)

AF:

0.469

AC:

18608

AN:

39708

Ashkenazi Jewish (ASJ)

AF:

0.308

AC:

7635

AN:

24820

East Asian (EAS)

AF:

0.279

AC:

10880

AN:

38948

South Asian (SAS)

AF:

0.248

AC:

20350

AN:

82106

European-Finnish (FIN)

AF:

0.435

AC:

22991

AN:

52820

Middle Eastern (MID)

AF:

0.315

AC:

1673

AN:

5308

European-Non Finnish (NFE)

AF:

0.343

AC:

372969

AN:

1087386

Other (OTH)

AF:

0.347

AC:

20273

AN:

58430

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

14356

28712

43068

57424

71780

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12292

24584

36876

49168

61460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.421

AC:

63973

AN:

152092

Hom.:

14206

Cov.:

AF XY:

0.424

AC XY:

31523

AN XY:

74348

show subpopulations

African (AFR)

AF:

0.569

AC:

23614

AN:

41486

American (AMR)

AF:

0.459

AC:

7013

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1075

AN:

3470

East Asian (EAS)

AF:

0.253

AC:

1304

AN:

5162

South Asian (SAS)

AF:

0.238

AC:

1149

AN:

4828

European-Finnish (FIN)

AF:

0.457

AC:

4830

AN:

10566

Middle Eastern (MID)

AF:

0.327

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.346

AC:

23544

AN:

67974

Other (OTH)

AF:

0.416

AC:

879

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1832

3664

5495

7327

9159

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

578

1156

1734

2312

2890

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.358

Hom.:

19519

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jul 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Congenital myasthenic syndrome 20

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Neuronopathy, distal hereditary motor, type 7A

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.15

(source)

DANN

Benign

0.61

PhyloP100

-0.71

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over