rs333226

Positions:

• chr2-108011461-G-A
• chr2-108011461-G-C
• chr2-108011461-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021815.5(SLC5A7):​c.*600G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.906 in 152,232 control chromosomes in the GnomAD database, including 62,743 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.91 (62743 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: SLC5A7 NM_021815.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.04

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.971 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC5A7	NM_021815.5	c.*600G>A		3_prime_UTR_variant	9/9	ENST00000264047.3	NP_068587.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC5A7	ENST00000264047.3	c.*600G>A		3_prime_UTR_variant	9/9	1	NM_021815.5	ENSP00000264047.2

Frequencies

GnomAD3 genomes AF: 0.906 AC: 137759 AN: 152114 Hom.: 62680 Cov.: 32

Gnomad AFR AF: 0.976

Gnomad AMI AF: 0.846

Gnomad AMR AF: 0.913

Gnomad ASJ AF: 0.783

Gnomad EAS AF: 0.994

Gnomad SAS AF: 0.873

Gnomad FIN AF: 0.948

Gnomad MID AF: 0.822

Gnomad NFE AF: 0.858

Gnomad OTH AF: 0.888

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.906 AC: 137882 AN: 152232 Hom.: 62743 Cov.: 32 AF XY: 0.910 AC XY: 67724 AN XY: 74432

Gnomad4 AFR AF: 0.976

Gnomad4 AMR AF: 0.914

Gnomad4 ASJ AF: 0.783

Gnomad4 EAS AF: 0.994

Gnomad4 SAS AF: 0.874

Gnomad4 FIN AF: 0.948

Gnomad4 NFE AF: 0.858

Gnomad4 OTH AF: 0.888

Alfa AF: 0.866 Hom.: 55002

Bravo AF: 0.908

Asia WGS AF: 0.938 AC: 3256 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.047
DANN	Benign	0.35

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs333226; hg19: chr2-108627917;