2-107987955-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_021815.5(SLC5A7):c.-51-150T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0496 in 435,132 control chromosomes in the GnomAD database, including 775 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.060 (358 hom., cov: 33)
  • Exomes 𝑓: 0.044 (417 hom.)
• Consequence: SLC5A7 NM_021815.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.548

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-107987955-T-C is Benign according to our data. Variant chr2-107987955-T-C is described in ClinVar as [Benign]. Clinvar id is 1295904.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.108 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A7	NM_021815.5	c.-51-150T>C		intron_variant		ENST00000264047.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A7	ENST00000264047.3	c.-51-150T>C		intron_variant		1	NM_021815.5	P1
SLC5A7	ENST00000409059.5	c.-48-153T>C		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.0604 AC: 9183 AN: 152140 Hom.: 358 Cov.: 33

Gnomad AFR AF: 0.0988

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.0518

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.0327

Gnomad SAS AF: 0.117

Gnomad FIN AF: 0.0525

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0385

Gnomad OTH AF: 0.0564

GnomAD4 exome AF: 0.0438 AC: 12381 AN: 282874 Hom.: 417 AF XY: 0.0448 AC XY: 6478 AN XY: 144676

Gnomad4 AFR exome AF: 0.0978

Gnomad4 AMR exome AF: 0.0356

Gnomad4 ASJ exome AF: 0.0428

Gnomad4 EAS exome AF: 0.0455

Gnomad4 SAS exome AF: 0.117

Gnomad4 FIN exome AF: 0.0535

Gnomad4 NFE exome AF: 0.0362

Gnomad4 OTH exome AF: 0.0432

GnomAD4 genome AF: 0.0603 AC: 9182 AN: 152258 Hom.: 358 Cov.: 33 AF XY: 0.0627 AC XY: 4668 AN XY: 74458

Gnomad4 AFR AF: 0.0988

Gnomad4 AMR AF: 0.0516

Gnomad4 ASJ AF: 0.0461

Gnomad4 EAS AF: 0.0324

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.0525

Gnomad4 NFE AF: 0.0385

Gnomad4 OTH AF: 0.0568

Alfa AF: 0.0546 Hom.: 39

Bravo AF: 0.0585

Asia WGS AF: 0.0860 AC: 298 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	7.2
Dann	Benign	0.55

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: rs13398078; hg19: chr2-108604411;