3-10872080-A-G

Variant names:

• chr3-10872080-A-G
• rs4684742
• NM_014229.3:c.757-2881A>G

Variant summary

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

The NM_014229.3(SLC6A11):​c.757-2881A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 152,054 control chromosomes in the GnomAD database, including 15,862 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 0.45 (15862 hom., cov: 33)
• Consequence: SLC6A11 NM_014229.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.14
• Publications: 6 publications found

Genes affected

SLC6A11 (HGNC:11044): (solute carrier family 6 member 11) The protein encoded by this gene is a sodium-dependent transporter that uptakes gamma-aminobutyric acid (GABA), an inhibitory neurotransmitter, which ends the GABA neurotransmission. Defects in this gene may result in epilepsy, behavioral problems, or intellectual problems. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2015]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.626 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A11	NM_014229.3	c.757-2881A>G		intron_variant	Intron 5 of 13	ENST00000254488.7	NP_055044.1
SLC6A11	XM_047448764.1	c.235-2881A>G		intron_variant	Intron 3 of 11		XP_047304720.1
SLC6A11	XM_011534033.3	c.757-2881A>G		intron_variant	Intron 5 of 8		XP_011532335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A11	ENST00000254488.7	c.757-2881A>G		intron_variant	Intron 5 of 13	1	NM_014229.3	ENSP00000254488.2

Frequencies

GnomAD3 genomes AF: 0.446 AC: 67766 AN: 151936 Hom.: 15817 Cov.: 33

Gnomad AFR AF: 0.536

Gnomad AMI AF: 0.462

Gnomad AMR AF: 0.475

Gnomad ASJ AF: 0.450

Gnomad EAS AF: 0.644

Gnomad SAS AF: 0.576

Gnomad FIN AF: 0.353

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.450

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

GnomAD4 genome AF: 0.446 AC: 67872 AN: 152054 Hom.: 15862 Cov.: 33 AF XY: 0.450 AC XY: 33476 AN XY: 74322

African (AFR) AF: 0.537 AC: 22269 AN: 41470

American (AMR) AF: 0.476 AC: 7270 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.450 AC: 1559 AN: 3468

East Asian (EAS) AF: 0.644 AC: 3334 AN: 5174

South Asian (SAS) AF: 0.576 AC: 2775 AN: 4816

European-Finnish (FIN) AF: 0.353 AC: 3728 AN: 10566

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25429 AN: 67966

Other (OTH) AF: 0.449 AC: 946 AN: 2106

Alfa AF: 0.409 Hom.: 17272

Bravo AF: 0.462

Asia WGS AF: 0.598 AC: 2081 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.57
DANN	Benign	0.86
PhyloP100		-1.1
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: rs4684742; hg19: chr3-10913765;