3-11008877-A-G

Variant names:

• chr3-11008877-A-G
• rs11710097
• NM_003042.4:c.-215-6795A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003042.4(SLC6A1):​c.-215-6795A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0489 in 152,332 control chromosomes in the GnomAD database, including 223 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 0.049 (223 hom., cov: 35)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.183
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.73).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0626 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003042.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A1	NM_003042.4	MANE Select	c.-215-6795A>G		intron	N/A	NP_003033.3
	SLC6A1	NM_001348250.2		c.-154-6795A>G		intron	N/A	NP_001335179.1
	SLC6A1	NM_001348251.2		c.-324-6795A>G		intron	N/A	NP_001335180.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A1	ENST00000287766.10	TSL:1 MANE Select	c.-215-6795A>G		intron	N/A	ENSP00000287766.4
	SLC6A1	ENST00000642201.1		c.-25-8310A>G		intron	N/A	ENSP00000494778.1
	SLC6A1	ENST00000642515.1		c.-1222-3722A>G		intron	N/A	ENSP00000496348.1

Frequencies

GnomAD3 genomes AF: 0.0489 AC: 7447 AN: 152214 Hom.: 223 Cov.: 35

Gnomad AFR AF: 0.0390

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0432

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.0285

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0641

Gnomad OTH AF: 0.0574

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

GnomAD4 genome AF: 0.0489 AC: 7456 AN: 152332 Hom.: 223 Cov.: 35 AF XY: 0.0462 AC XY: 3442 AN XY: 74492

African (AFR) AF: 0.0390 AC: 1621 AN: 41578

American (AMR) AF: 0.0431 AC: 660 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 301 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5186

South Asian (SAS) AF: 0.0120 AC: 58 AN: 4830

European-Finnish (FIN) AF: 0.0285 AC: 303 AN: 10618

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0641 AC: 4363 AN: 68022

Other (OTH) AF: 0.0568 AC: 120 AN: 2114

Alfa AF: 0.0620 Hom.: 199

Bravo AF: 0.0509

Asia WGS AF: 0.0160 AC: 55 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	4.0
DANN	Benign	0.86
PhyloP100		0.18
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs11710097; hg19: chr3-11050563;