rs11712912

Positions:

• chr3-11021859-G-A

Variant summary

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

The NM_003042.4(SLC6A1):​c.582-477G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0907 in 154,990 control chromosomes in the GnomAD database, including 722 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 0.091 (707 hom., cov: 33)
  • Exomes 𝑓: 0.081 (15 hom.)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

Genes affected

SLC6A1 (HGNC:11042): (solute carrier family 6 member 1) The protein encoded by this gene is a gamma-aminobutyric acid (GABA) transporter that localizes to the plasma membrane. The encoded protein removes GABA from the synaptic cleft, restoring it to presynaptic terminals. [provided by RefSeq, Jan 2017]

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 = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A1	NM_003042.4	c.582-477G>A		intron_variant		ENST00000287766.10	NP_003033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10	c.582-477G>A		intron_variant		1	NM_003042.4	ENSP00000287766	P1

Frequencies

GnomAD3 genomes AF: 0.0909 AC: 13834 AN: 152166 Hom.: 703 Cov.: 33

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.0493

Gnomad AMR AF: 0.0704

Gnomad ASJ AF: 0.134

Gnomad EAS AF: 0.0999

Gnomad SAS AF: 0.121

Gnomad FIN AF: 0.0448

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0987

Gnomad OTH AF: 0.108

GnomAD4 exome AF: 0.0813 AC: 220 AN: 2706 Hom.: 15 Cov.: 0 AF XY: 0.0688 AC XY: 108 AN XY: 1570

Gnomad4 AFR exome AF: 0.0909

Gnomad4 AMR exome AF: 0.0278

Gnomad4 ASJ exome AF: 0.119

Gnomad4 EAS exome AF: 0.0278

Gnomad4 SAS exome AF: 0.0645

Gnomad4 FIN exome AF: 0.0789

Gnomad4 NFE exome AF: 0.0843

Gnomad4 OTH exome AF: 0.0959

GnomAD4 genome AF: 0.0909 AC: 13841 AN: 152284 Hom.: 707 Cov.: 33 AF XY: 0.0891 AC XY: 6633 AN XY: 74474

Gnomad4 AFR AF: 0.0892

Gnomad4 AMR AF: 0.0703

Gnomad4 ASJ AF: 0.134

Gnomad4 EAS AF: 0.0996

Gnomad4 SAS AF: 0.121

Gnomad4 FIN AF: 0.0448

Gnomad4 NFE AF: 0.0988

Gnomad4 OTH AF: 0.109

Alfa AF: 0.101 Hom.: 746

Bravo AF: 0.0922

Asia WGS AF: 0.109 AC: 380 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	0.82
DANN	Benign	0.33

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: rs11712912; hg19: chr3-11063545;