rs17466478

Positions:

• chr3-11008832-C-T

Variant summary

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

The NM_003042.4(SLC6A1):​c.-215-6840C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 152,298 control chromosomes in the GnomAD database, including 428 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 0.061 (428 hom., cov: 35)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.994

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]

SLC6A1-AS1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.092 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A1	NM_003042.4	c.-215-6840C>T		intron_variant		ENST00000287766.10	NP_003033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10	c.-215-6840C>T		intron_variant		1	NM_003042.4	ENSP00000287766.4

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9357 AN: 152180 Hom.: 429 Cov.: 35

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0663

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0614 AC: 9345 AN: 152298 Hom.: 428 Cov.: 35 AF XY: 0.0586 AC XY: 4365 AN XY: 74458

Gnomad4 AFR AF: 0.0173

Gnomad4 AMR AF: 0.0662

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0377

Gnomad4 FIN AF: 0.0335

Gnomad4 NFE AF: 0.0939

Gnomad4 OTH AF: 0.0738

Alfa AF: 0.0841 Hom.: 397

Bravo AF: 0.0628

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
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: rs17466478; hg19: chr3-11050518;