rs4684746

Positions:

• chr3-10924903-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014229.3(SLC6A11):​c.1121-1101A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.148 in 152,244 control chromosomes in the GnomAD database, including 2,236 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 0.15 (2236 hom., cov: 33)
• Consequence: SLC6A11 NM_014229.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.55

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.31 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A11	NM_014229.3	c.1121-1101A>G		intron_variant		ENST00000254488.7	NP_055044.1
LOC105376950	XR_940587.3	n.1869+1954T>C		intron_variant, non_coding_transcript_variant
SLC6A11	XM_011534033.3	c.*959A>G		3_prime_UTR_variant	9/9		XP_011532335.1
SLC6A11	XM_047448764.1	c.599-1101A>G		intron_variant			XP_047304720.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A11	ENST00000254488.7	c.1121-1101A>G		intron_variant		1	NM_014229.3	ENSP00000254488	P1
	ENST00000656787.1	n.351-9531T>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.148 AC: 22551 AN: 152126 Hom.: 2224 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.0625

Gnomad AMR AF: 0.317

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.302

Gnomad SAS AF: 0.219

Gnomad FIN AF: 0.163

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.111

Gnomad OTH AF: 0.142

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

GnomAD4 genome AF: 0.148 AC: 22602 AN: 152244 Hom.: 2236 Cov.: 33 AF XY: 0.155 AC XY: 11562 AN XY: 74456

Gnomad4 AFR AF: 0.127

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.0588

Gnomad4 EAS AF: 0.303

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.163

Gnomad4 NFE AF: 0.111

Gnomad4 OTH AF: 0.142

Alfa AF: 0.124 Hom.: 2366

Bravo AF: 0.161

Asia WGS AF: 0.274 AC: 949 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.020
DANN	Benign	0.46

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: rs4684746; hg19: chr3-10966588;