3-11007447-C-T

Variant names:

• chr3-11007447-C-T
• rs1710891
• NM_003042.4:c.-215-8225C>T

Variant summary

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

The NM_003042.4(SLC6A1):​c.-215-8225C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,178 control chromosomes in the GnomAD database, including 11,433 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 0.38 (11422 hom., cov: 33)
  • Exomes 𝑓: 0.51 (11 hom.)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

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:40546): (SLC6A1 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4	c.-215-8225C>T		intron_variant	Intron 1 of 15	ENST00000287766.10	NP_003033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10	c.-215-8225C>T		intron_variant	Intron 1 of 15	1	NM_003042.4	ENSP00000287766.4

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58308 AN: 151980 Hom.: 11411 Cov.: 33

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.512 AC: 41 AN: 80 Hom.: 11 AF XY: 0.441 AC XY: 30 AN XY: 68

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 1.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.485

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.384 AC: 58355 AN: 152098 Hom.: 11422 Cov.: 33 AF XY: 0.383 AC XY: 28443 AN XY: 74346

Gnomad4 AFR AF: 0.404

Gnomad4 AMR AF: 0.296

Gnomad4 ASJ AF: 0.381

Gnomad4 EAS AF: 0.463

Gnomad4 SAS AF: 0.392

Gnomad4 FIN AF: 0.365

Gnomad4 NFE AF: 0.387

Gnomad4 OTH AF: 0.388

Alfa AF: 0.379 Hom.: 6185

Bravo AF: 0.378

Asia WGS AF: 0.410 AC: 1425 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.64
DANN	Benign	0.53

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: rs1710891; hg19: chr3-11049133;