3-11016816-T-C

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.-153-243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 152,188 control chromosomes in the GnomAD database, including 1,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.088 (1564 hom., cov: 32)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.562

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=-0.89).
• BP6: Variant 3-11016816-T-C is Benign according to our data. Variant chr3-11016816-T-C is described in ClinVar as [Benign]. Clinvar id is 1288263.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A1	NM_003042.4	c.-153-243T>C		intron_variant		ENST00000287766.10
SLC6A1-AS1	NR_046647.1	n.105+2304A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A1	ENST00000287766.10	c.-153-243T>C		intron_variant		1	NM_003042.4	P1
SLC6A1-AS1	ENST00000414969.2	n.105+2304A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13355 AN: 152070 Hom.: 1557 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00813

Gnomad OTH AF: 0.0645

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

GnomAD4 genome AF: 0.0880 AC: 13394 AN: 152188 Hom.: 1564 Cov.: 32 AF XY: 0.0864 AC XY: 6429 AN XY: 74396

Gnomad4 AFR AF: 0.268

Gnomad4 AMR AF: 0.0469

Gnomad4 ASJ AF: 0.0433

Gnomad4 EAS AF: 0.0896

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.00104

Gnomad4 NFE AF: 0.00813

Gnomad4 OTH AF: 0.0633

Alfa AF: 0.0404 Hom.: 138

Bravo AF: 0.100

Asia WGS AF: 0.0700 AC: 243 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

Jul 15, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	3.6
Dann	Benign	0.65

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: rs11923810; hg19: chr3-11058502;