rs11715462

Positions:

• chr3-10888335-A-T

Variant summary

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

The NM_014229.3(SLC6A11):​c.891+13240A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.144 in 152,194 control chromosomes in the GnomAD database, including 2,217 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 0.14 (2217 hom., cov: 32)
• Consequence: SLC6A11 NM_014229.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.277 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A11	NM_014229.3	c.891+13240A>T		intron_variant		ENST00000254488.7
SLC6A11	XM_011534033.3	c.891+13240A>T		intron_variant
SLC6A11	XM_047448764.1	c.369+13240A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A11	ENST00000254488.7	c.891+13240A>T		intron_variant		1	NM_014229.3	P1

Frequencies

GnomAD3 genomes AF: 0.144 AC: 21928 AN: 152076 Hom.: 2216 Cov.: 32

Gnomad AFR AF: 0.281

Gnomad AMI AF: 0.0934

Gnomad AMR AF: 0.0804

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.212

Gnomad SAS AF: 0.191

Gnomad FIN AF: 0.0626

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0839

Gnomad OTH AF: 0.127

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

GnomAD4 genome AF: 0.144 AC: 21947 AN: 152194 Hom.: 2217 Cov.: 32 AF XY: 0.143 AC XY: 10678 AN XY: 74414

Gnomad4 AFR AF: 0.281

Gnomad4 AMR AF: 0.0802

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.212

Gnomad4 SAS AF: 0.191

Gnomad4 FIN AF: 0.0626

Gnomad4 NFE AF: 0.0839

Gnomad4 OTH AF: 0.128

Alfa AF: 0.113 Hom.: 168

Bravo AF: 0.153

Asia WGS AF: 0.215 AC: 748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.0
DANN	Benign	0.46

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: rs11715462; hg19: chr3-10930020;