rs1610180

Positions:

• chr3-10875772-A-C
• chr3-10875772-A-G
• chr3-10875772-A-T

Variant summary

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

The NM_014229.3(SLC6A11):​c.891+677A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 152,050 control chromosomes in the GnomAD database, including 25,841 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 0.56 (25841 hom., cov: 32)
• Consequence: SLC6A11 NM_014229.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.115

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.76 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC6A11	NM_014229.3	c.891+677A>C		intron_variant		ENST00000254488.7	NP_055044.1
SLC6A11	XM_047448764.1	c.369+677A>C		intron_variant			XP_047304720.1
SLC6A11	XM_011534033.3	c.891+677A>C		intron_variant			XP_011532335.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC6A11	ENST00000254488.7	c.891+677A>C		intron_variant		1	NM_014229.3	ENSP00000254488.2

Frequencies

GnomAD3 genomes AF: 0.561 AC: 85222 AN: 151930 Hom.: 25795 Cov.: 32

Gnomad AFR AF: 0.767

Gnomad AMI AF: 0.510

Gnomad AMR AF: 0.550

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.755

Gnomad FIN AF: 0.373

Gnomad MID AF: 0.587

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.558

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

GnomAD4 genome AF: 0.561 AC: 85329 AN: 152050 Hom.: 25841 Cov.: 32 AF XY: 0.564 AC XY: 41942 AN XY: 74332

Gnomad4 AFR AF: 0.767

Gnomad4 AMR AF: 0.550

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.762

Gnomad4 SAS AF: 0.755

Gnomad4 FIN AF: 0.373

Gnomad4 NFE AF: 0.439

Gnomad4 OTH AF: 0.555

Alfa AF: 0.472 Hom.: 16229

Bravo AF: 0.584

Asia WGS AF: 0.742 AC: 2582 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.7
DANN	Benign	0.42

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: rs1610180; hg19: chr3-10917457;