rs1809529

Positions:

• chr3-10835926-C-T

Variant summary

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

The NM_014229.3(SLC6A11):​c.624-8288C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.448 in 152,106 control chromosomes in the GnomAD database, including 17,479 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 0.45 (17479 hom., cov: 33)
• Consequence: SLC6A11 NM_014229.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.348

Genes affected

SLC6A11 (HGNC:11044): (solute carrier family 6 member 11) The protein encoded by this gene is a sodium-dependent transporter that uptakes gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which ends the GABA neurotransmission. Defects in this gene may result in epilepsy, behavioral problems, or intellectual problems. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.697 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A11	NM_014229.3	c.624-8288C>T		intron_variant		ENST00000254488.7	NP_055044.1
SLC6A11	XM_047448764.1	c.47-5013C>T		intron_variant			XP_047304720.1
SLC6A11	XM_011534033.3	c.624-8288C>T		intron_variant			XP_011532335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A11	ENST00000254488.7	c.624-8288C>T		intron_variant		1	NM_014229.3	ENSP00000254488.2

Frequencies

GnomAD3 genomes AF: 0.448 AC: 68116 AN: 151986 Hom.: 17445 Cov.: 33

Gnomad AFR AF: 0.704

Gnomad AMI AF: 0.408

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.402

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.618

Gnomad FIN AF: 0.312

Gnomad MID AF: 0.497

Gnomad NFE AF: 0.336

Gnomad OTH AF: 0.428

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

GnomAD4 genome AF: 0.448 AC: 68192 AN: 152106 Hom.: 17479 Cov.: 33 AF XY: 0.451 AC XY: 33526 AN XY: 74358

Gnomad4 AFR AF: 0.704

Gnomad4 AMR AF: 0.305

Gnomad4 ASJ AF: 0.402

Gnomad4 EAS AF: 0.460

Gnomad4 SAS AF: 0.619

Gnomad4 FIN AF: 0.312

Gnomad4 NFE AF: 0.336

Gnomad4 OTH AF: 0.424

Alfa AF: 0.351 Hom.: 16340

Bravo AF: 0.456

Asia WGS AF: 0.517 AC: 1801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.99
DANN	Benign	0.58

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: rs1809529; hg19: chr3-10877611;