3-11016978-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_003042.4(SLC6A1):c.-153-81C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00841 in 539,788 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.016 (49 hom., cov: 32)
  • Exomes 𝑓: 0.0054 (41 hom.)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.649

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 3-11016978-C-T is Benign according to our data. Variant chr3-11016978-C-T is described in ClinVar as [Benign]. Clinvar id is 1226679.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0161 (2447/152182) while in subpopulation AFR AF= 0.0503 (2089/41498). AF 95% confidence interval is 0.0485. There are 49 homozygotes in gnomad4. There are 1213 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd at 2445 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A1	NM_003042.4	c.-153-81C>T		intron_variant		ENST00000287766.10
SLC6A1-AS1	NR_046647.1	n.105+2142G>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A1	ENST00000287766.10	c.-153-81C>T		intron_variant		1	NM_003042.4	P1
SLC6A1-AS1	ENST00000414969.2	n.105+2142G>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2445 AN: 152064 Hom.: 48 Cov.: 32

Gnomad AFR AF: 0.0504

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00688

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00944

Gnomad SAS AF: 0.0256

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000470

Gnomad OTH AF: 0.0144

GnomAD4 exome AF: 0.00540 AC: 2095 AN: 387606 Hom.: 41 AF XY: 0.00607 AC XY: 1230 AN XY: 202652

Gnomad4 AFR exome AF: 0.0504

Gnomad4 AMR exome AF: 0.00379

Gnomad4 ASJ exome AF: 0.00450

Gnomad4 EAS exome AF: 0.0102

Gnomad4 SAS exome AF: 0.0225

Gnomad4 FIN exome AF: 0.0000812

Gnomad4 NFE exome AF: 0.000309

Gnomad4 OTH exome AF: 0.00685

GnomAD4 genome AF: 0.0161 AC: 2447 AN: 152182 Hom.: 49 Cov.: 32 AF XY: 0.0163 AC XY: 1213 AN XY: 74394

Gnomad4 AFR AF: 0.0503

Gnomad4 AMR AF: 0.00687

Gnomad4 ASJ AF: 0.00461

Gnomad4 EAS AF: 0.00946

Gnomad4 SAS AF: 0.0256

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000471

Gnomad4 OTH AF: 0.0142

Alfa AF: 0.00969 Hom.: 1

Bravo AF: 0.0180

Asia WGS AF: 0.0320 AC: 112 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 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	8.1
Dann	Benign	0.57

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs41388950; hg19: chr3-11058664;