3-11015683-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003042.4(SLC6A1):c.-204G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.468 in 152,160 control chromosomes in the GnomAD database, including 17,991 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (17973 hom., cov: 33)
  • Exomes 𝑓: 0.57 (18 hom.)
• Consequence: SLC6A1 NM_003042.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.451

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 3-11015683-G-A is Benign according to our data. Variant chr3-11015683-G-A is described in ClinVar as [Benign]. Clinvar id is 1246526.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.567 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A1	NM_003042.4	c.-204G>A		5_prime_UTR_variant	2/16	ENST00000287766.10
SLC6A1-AS1	NR_046647.1	n.105+3437C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A1	ENST00000287766.10	c.-204G>A		5_prime_UTR_variant	2/16	1	NM_003042.4	P1
SLC6A1-AS1	ENST00000414969.2	n.105+3437C>T		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.468 AC: 71136 AN: 151920 Hom.: 17960 Cov.: 33

Gnomad AFR AF: 0.279

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.577

Gnomad ASJ AF: 0.446

Gnomad EAS AF: 0.396

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.472

Gnomad NFE AF: 0.551

Gnomad OTH AF: 0.472

GnomAD4 exome AF: 0.566 AC: 69 AN: 122 Hom.: 18 Cov.: 0 AF XY: 0.598 AC XY: 49 AN XY: 82

Gnomad4 FIN exome AF: 0.538

Gnomad4 NFE exome AF: 0.525

Gnomad4 OTH exome AF: 0.813

GnomAD4 genome AF: 0.468 AC: 71177 AN: 152038 Hom.: 17973 Cov.: 33 AF XY: 0.469 AC XY: 34828 AN XY: 74314

Gnomad4 AFR AF: 0.279

Gnomad4 AMR AF: 0.577

Gnomad4 ASJ AF: 0.446

Gnomad4 EAS AF: 0.397

Gnomad4 SAS AF: 0.386

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.551

Gnomad4 OTH AF: 0.478

Alfa AF: 0.486 Hom.: 2787

Bravo AF: 0.459

Asia WGS AF: 0.402 AC: 1400 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Dec 19, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
Cadd	Benign	6.0
Dann	Benign	0.79

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: rs6342; hg19: chr3-11057369;