rs4923627

Positions:

• chr11-20642857-G-A

Variant summary

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

The ENST00000525748.6(SLC6A5):​c.1970-3977G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,138 control chromosomes in the GnomAD database, including 6,597 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 0.28 (6597 hom., cov: 31)
• Consequence: SLC6A5 ENST00000525748.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.69

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 (NFE) allele frequency at 95% confidence interval = 0.353 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A5	NM_004211.5	c.1970-3977G>A		intron_variant		ENST00000525748.6	NP_004202.4
SLC6A5	NM_001318369.2	c.1268-3977G>A		intron_variant			NP_001305298.1
SLC6A5	XM_017018544.3	c.1094-3977G>A		intron_variant			XP_016874033.1
SLC6A5	XR_007062528.1	n.1348-3977G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A5	ENST00000525748.6	c.1970-3977G>A		intron_variant		1	NM_004211.5	ENSP00000434364	P1
SLC6A5	ENST00000298923.11	c.*1267-3977G>A		intron_variant, NMD_transcript_variant		1		ENSP00000298923
SLC6A5	ENST00000528440.1	n.501-3977G>A		intron_variant, non_coding_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42904 AN: 152020 Hom.: 6599 Cov.: 31

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.481

Gnomad AMR AF: 0.214

Gnomad ASJ AF: 0.254

Gnomad EAS AF: 0.00694

Gnomad SAS AF: 0.223

Gnomad FIN AF: 0.279

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.282 AC: 42906 AN: 152138 Hom.: 6597 Cov.: 31 AF XY: 0.272 AC XY: 20241 AN XY: 74364

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.254

Gnomad4 EAS AF: 0.00715

Gnomad4 SAS AF: 0.223

Gnomad4 FIN AF: 0.279

Gnomad4 NFE AF: 0.357

Gnomad4 OTH AF: 0.284

Alfa AF: 0.334 Hom.: 14945

Bravo AF: 0.279

Asia WGS AF: 0.116 AC: 405 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	0.35
DANN	Benign	0.54

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: rs4923627; hg19: chr11-20664403;