2-107987962-C-T

Position:

• chr2-107987962-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
SLC5A7	NM_021815.5	c.-51-143C>T		intron_variant		ENST00000264047.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A7	ENST00000264047.3	c.-51-143C>T		intron_variant		1	NM_021815.5	P1
SLC5A7	ENST00000409059.5	c.-48-146C>T		intron_variant		1		P1

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

Gnomad4 AFR exome AF: 0.100

Gnomad4 AMR exome AF: 0.0378

Gnomad4 ASJ exome AF: 0.0470

Gnomad4 EAS exome AF: 0.0489

Gnomad4 SAS exome AF: 0.122

Gnomad4 FIN exome AF: 0.0601

Gnomad4 NFE exome AF: 0.0393

Gnomad4 OTH exome AF: 0.0452

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

Gnomad4 AFR AF: 0.0954

Gnomad4 AMR AF: 0.0519

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.0325

Gnomad4 SAS AF: 0.117

Gnomad4 FIN AF: 0.0528

Gnomad4 NFE AF: 0.0385

Gnomad4 OTH AF: 0.0568

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 17, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.1
DANN	Benign	0.52

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

Other links and lift over

dbSNP: rs13384641; hg19: chr2-108604418;