rs3758807

Positions:

• chr11-20616985-G-A
• chr11-20616985-G-T

Variant summary

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

The NM_004211.5(SLC6A5):​c.1128-767G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 152,046 control chromosomes in the GnomAD database, including 11,537 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 0.39 (11537 hom., cov: 33)
• Consequence: SLC6A5 NM_004211.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.454

Genes affected

SLC6A5 (HGNC:11051): (solute carrier family 6 member 5) This gene encodes a sodium- and chloride-dependent glycine neurotransmitter transporter. This integral membrane glycoprotein is responsible for the clearance of extracellular glycine during glycine-mediated neurotransmission. This protein is found in glycinergic axons and maintains a high presynaptic pool of neurotransmitter at glycinergic synapses. Mutations in this gene cause hyperekplexia; a heterogenous neurological disorder characterized by exaggerated startle responses and neonatal apnea. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.494 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A5	NM_004211.5	c.1128-767G>A		intron_variant		ENST00000525748.6	NP_004202.4
SLC6A5	NM_001318369.2	c.426-767G>A		intron_variant			NP_001305298.1
SLC6A5	XM_017018544.3	c.252-767G>A		intron_variant			XP_016874033.1
SLC6A5	XR_007062528.1	n.506-767G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A5	ENST00000525748.6	c.1128-767G>A		intron_variant		1	NM_004211.5	ENSP00000434364	P1
SLC6A5	ENST00000298923.11	c.*425-767G>A		intron_variant, NMD_transcript_variant		1		ENSP00000298923

Frequencies

GnomAD3 genomes AF: 0.387 AC: 58836 AN: 151928 Hom.: 11529 Cov.: 33

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.343

Gnomad AMR AF: 0.385

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.510

Gnomad FIN AF: 0.372

Gnomad MID AF: 0.364

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.391

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

GnomAD4 genome AF: 0.387 AC: 58861 AN: 152046 Hom.: 11537 Cov.: 33 AF XY: 0.390 AC XY: 28992 AN XY: 74304

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.384

Gnomad4 ASJ AF: 0.365

Gnomad4 EAS AF: 0.301

Gnomad4 SAS AF: 0.511

Gnomad4 FIN AF: 0.372

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.395

Alfa AF: 0.388 Hom.: 6351

Bravo AF: 0.386

Asia WGS AF: 0.433 AC: 1503 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.20
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: rs3758807; hg19: chr11-20638531;