2-107987955-T-C

Variant names:

• chr2-107987955-T-C
• rs13398078
• NM_021815.5:c.-51-150T>C

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.-51-150T>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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.548
• Publications: 0 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=-0.82).
• 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_multiple_submitters_no_conflicts, 2 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 rank	MANE	Protein	UniProt
SLC5A7	NM_021815.5	c.-51-150T>C		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.-51-150T>C		intron_variant	Intron 1 of 8	1	NM_021815.5	ENSP00000264047.2
SLC5A7	ENST00000409059.5	c.-48-153T>C		intron_variant	Intron 1 of 8	1		ENSP00000387346.1

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

African (AFR) AF: 0.0978 AC: 953 AN: 9742

American (AMR) AF: 0.0356 AC: 413 AN: 11590

Ashkenazi Jewish (ASJ) AF: 0.0428 AC: 428 AN: 10008

East Asian (EAS) AF: 0.0455 AC: 1165 AN: 25630

South Asian (SAS) AF: 0.117 AC: 1096 AN: 9352

European-Finnish (FIN) AF: 0.0535 AC: 1123 AN: 21008

Middle Eastern (MID) AF: 0.0334 AC: 47 AN: 1406

European-Non Finnish (NFE) AF: 0.0362 AC: 6376 AN: 176066

Other (OTH) AF: 0.0432 AC: 780 AN: 18072

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

African (AFR) AF: 0.0988 AC: 4103 AN: 41538

American (AMR) AF: 0.0516 AC: 790 AN: 15302

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

East Asian (EAS) AF: 0.0324 AC: 168 AN: 5188

South Asian (SAS) AF: 0.116 AC: 560 AN: 4820

European-Finnish (FIN) AF: 0.0525 AC: 557 AN: 10610

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

European-Non Finnish (NFE) AF: 0.0385 AC: 2621 AN: 68010

Other (OTH) AF: 0.0568 AC: 120 AN: 2114

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: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	-0.82
CADD	Benign	7.2
DANN	Benign	0.55
PhyloP100		0.55
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: rs13398078; hg19: chr2-108604411;