2-107987962-C-T

Variant names:

• chr2-107987962-C-T
• rs13384641
• NM_021815.5:c.-51-143C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_021815.5(SLC5A7):​c.-51-143C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0517 in 424,650 control chromosomes in the GnomAD database, including 776 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.059 (346 hom., cov: 33)
  • Exomes 𝑓: 0.047 (430 hom.)
• Consequence: SLC5A7 NM_021815.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.648
• Publications: 1 publications found

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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-107987962-C-T is Benign according to our data. Variant chr2-107987962-C-T is described in ClinVar as [Benign]. Clinvar id is 1295903.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.109 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC5A7	NM_021815.5	c.-51-143C>T		intron_variant	Intron 1 of 8	ENST00000264047.3	NP_068587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC5A7	ENST00000264047.3	c.-51-143C>T		intron_variant	Intron 1 of 8	1	NM_021815.5	ENSP00000264047.2
SLC5A7	ENST00000409059.5	c.-48-146C>T		intron_variant	Intron 1 of 8	1		ENSP00000387346.1

Frequencies

GnomAD3 genomes AF: 0.0595 AC: 9039 AN: 151802 Hom.: 348 Cov.: 33

Gnomad AFR AF: 0.0957

Gnomad AMI AF: 0.0989

Gnomad AMR AF: 0.0521

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.0328

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0385

Gnomad OTH AF: 0.0565

GnomAD4 exome AF: 0.0473 AC: 12906 AN: 272724 Hom.: 430 AF XY: 0.0486 AC XY: 6804 AN XY: 139996

African (AFR) AF: 0.100 AC: 942 AN: 9374

American (AMR) AF: 0.0378 AC: 428 AN: 11316

Ashkenazi Jewish (ASJ) AF: 0.0470 AC: 443 AN: 9432

East Asian (EAS) AF: 0.0489 AC: 1200 AN: 24516

South Asian (SAS) AF: 0.122 AC: 1202 AN: 9816

European-Finnish (FIN) AF: 0.0601 AC: 1196 AN: 19894

Middle Eastern (MID) AF: 0.0368 AC: 50 AN: 1360

European-Non Finnish (NFE) AF: 0.0393 AC: 6666 AN: 169772

Other (OTH) AF: 0.0452 AC: 779 AN: 17244

GnomAD4 genome AF: 0.0594 AC: 9029 AN: 151926 Hom.: 346 Cov.: 33 AF XY: 0.0620 AC XY: 4602 AN XY: 74250

African (AFR) AF: 0.0954 AC: 3953 AN: 41426

American (AMR) AF: 0.0519 AC: 792 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3470

East Asian (EAS) AF: 0.0325 AC: 167 AN: 5134

South Asian (SAS) AF: 0.117 AC: 558 AN: 4786

European-Finnish (FIN) AF: 0.0528 AC: 557 AN: 10554

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0385 AC: 2619 AN: 67968

Other (OTH) AF: 0.0568 AC: 120 AN: 2112

Alfa AF: 0.0540 Hom.: 39

Bravo AF: 0.0572

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 17, 2018

GeneDx

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	-0.86
CADD	Benign	1.1
DANN	Benign	0.52
PhyloP100		-0.65
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs13384641; hg19: chr2-108604418;