rs333214

chr2-107995735-A-G

Variant summary

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

The NM_021815.5(SLC5A7):c.449-2103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.116 in 152,172 control chromosomes in the GnomAD database, including 1,182 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 0.12 (1182 hom., cov: 32)
• Consequence: SLC5A7 NM_021815.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.23

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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.137 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC5A7	NM_021815.5	c.449-2103A>G		intron_variant		ENST00000264047.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC5A7	ENST00000264047.3	c.449-2103A>G		intron_variant		1	NM_021815.5	P1
SLC5A7	ENST00000409059.5	c.449-2103A>G		intron_variant		1		P1

Frequencies

GnomAD3 genomes AF: 0.116 AC: 17668 AN: 152054 Hom.: 1181 Cov.: 32

Gnomad AFR AF: 0.0619

Gnomad AMI AF: 0.109

Gnomad AMR AF: 0.130

Gnomad ASJ AF: 0.136

Gnomad EAS AF: 0.0264

Gnomad SAS AF: 0.0812

Gnomad FIN AF: 0.209

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.146

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.116 AC: 17666 AN: 152172 Hom.: 1182 Cov.: 32 AF XY: 0.119 AC XY: 8833 AN XY: 74400

Gnomad4 AFR AF: 0.0619

Gnomad4 AMR AF: 0.130

Gnomad4 ASJ AF: 0.136

Gnomad4 EAS AF: 0.0264

Gnomad4 SAS AF: 0.0810

Gnomad4 FIN AF: 0.209

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.144

Alfa AF: 0.122 Hom.: 355

Bravo AF: 0.108

Asia WGS AF: 0.0540 AC: 190 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
Cadd	Benign	5.2
Dann	Benign	0.89

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: rs333214; hg19: chr2-108612191;