chr3-11016994-G-C

Position:

• chr3-11016994-G-C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003042.4(SLC6A1):​c.-153-65G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0558 in 569,292 control chromosomes in the GnomAD database, including 2,978 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (1936 hom., cov: 32)
  • Exomes 𝑓: 0.038 (1042 hom.)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0270

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 3-11016994-G-C is Benign according to our data. Variant chr3-11016994-G-C is described in ClinVar as [Benign]. Clinvar id is 1272282.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.292 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC6A1	NM_003042.4	c.-153-65G>C		intron_variant		ENST00000287766.10
SLC6A1-AS1	NR_046647.1	n.105+2126C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC6A1	ENST00000287766.10	c.-153-65G>C		intron_variant		1	NM_003042.4	P1
SLC6A1-AS1	ENST00000414969.2	n.105+2126C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15692 AN: 151896 Hom.: 1929 Cov.: 32

Gnomad AFR AF: 0.297

Gnomad AMI AF: 0.104

Gnomad AMR AF: 0.0699

Gnomad ASJ AF: 0.0444

Gnomad EAS AF: 0.0897

Gnomad SAS AF: 0.0496

Gnomad FIN AF: 0.0135

Gnomad MID AF: 0.0728

Gnomad NFE AF: 0.0158

Gnomad OTH AF: 0.0826

GnomAD4 exome AF: 0.0384 AC: 16010 AN: 417280 Hom.: 1042 AF XY: 0.0375 AC XY: 8226 AN XY: 219100

Gnomad4 AFR exome AF: 0.303

Gnomad4 AMR exome AF: 0.0500

Gnomad4 ASJ exome AF: 0.0454

Gnomad4 EAS exome AF: 0.118

Gnomad4 SAS exome AF: 0.0441

Gnomad4 FIN exome AF: 0.00941

Gnomad4 NFE exome AF: 0.0166

Gnomad4 OTH exome AF: 0.0492

GnomAD4 genome AF: 0.103 AC: 15732 AN: 152012 Hom.: 1936 Cov.: 32 AF XY: 0.103 AC XY: 7625 AN XY: 74306

Gnomad4 AFR AF: 0.297

Gnomad4 AMR AF: 0.0701

Gnomad4 ASJ AF: 0.0444

Gnomad4 EAS AF: 0.0899

Gnomad4 SAS AF: 0.0499

Gnomad4 FIN AF: 0.0135

Gnomad4 NFE AF: 0.0158

Gnomad4 OTH AF: 0.0813

Alfa AF: 0.0171 Hom.: 40

Bravo AF: 0.118

Asia WGS AF: 0.0730 AC: 252 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
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	-0.84
CADD	Benign	2.2
DANN	Benign	0.54

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: rs11919775; hg19: chr3-11058680;