rs1919075

Positions:

• chr3-11001333-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.-216+8404G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,216 control chromosomes in the GnomAD database, including 5,971 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 0.25 (5967 hom., cov: 32)
  • Exomes 𝑓: 0.26 (4 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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A1	NM_003042.4	c.-216+8404G>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.-216+8404G>A		intron_variant		1	NM_003042.4	ENSP00000287766	P1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38046 AN: 151990 Hom.: 5961 Cov.: 32

Gnomad AFR AF: 0.0698

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.423

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.192

Gnomad SAS AF: 0.289

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.313

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.269

GnomAD4 exome AF: 0.259 AC: 28 AN: 108 Hom.: 4 Cov.: 0 AF XY: 0.329 AC XY: 23 AN XY: 70

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.500

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.192

Gnomad4 NFE exome AF: 0.306

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.250 AC: 38059 AN: 152108 Hom.: 5967 Cov.: 32 AF XY: 0.253 AC XY: 18776 AN XY: 74352

Gnomad4 AFR AF: 0.0697

Gnomad4 AMR AF: 0.423

Gnomad4 ASJ AF: 0.282

Gnomad4 EAS AF: 0.193

Gnomad4 SAS AF: 0.289

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.272

Alfa AF: 0.308 Hom.: 2979

Bravo AF: 0.253

Asia WGS AF: 0.235 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.1
DANN	Benign	0.69

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: rs1919075; hg19: chr3-11043019;