rs17466478

Variant names:

• chr3-11008832-C-T
• rs17466478
• NM_003042.4:c.-215-6840C>T

Variant summary

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

The NM_003042.4(SLC6A1):​c.-215-6840C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0614 in 152,298 control chromosomes in the GnomAD database, including 428 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 0.061 (428 hom., cov: 35)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.994
• Publications: 2 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=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.092 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A1	NM_003042.4	MANE Select	c.-215-6840C>T		intron	N/A	NP_003033.3
	SLC6A1	NM_001348250.2		c.-154-6840C>T		intron	N/A	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.-324-6840C>T		intron	N/A	NP_001335180.1	A0A2R8Y4I3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A1	ENST00000287766.10	TSL:1 MANE Select	c.-215-6840C>T		intron	N/A	ENSP00000287766.4	P30531
	SLC6A1	ENST00000642201.1		c.-25-8355C>T		intron	N/A	ENSP00000494778.1	P30531
	SLC6A1	ENST00000642515.1		c.-1222-3767C>T		intron	N/A	ENSP00000496348.1	P30531

Frequencies

GnomAD3 genomes AF: 0.0615 AC: 9357 AN: 152180 Hom.: 429 Cov.: 35

Gnomad AFR AF: 0.0174

Gnomad AMI AF: 0.115

Gnomad AMR AF: 0.0663

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0381

Gnomad FIN AF: 0.0335

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.0939

Gnomad OTH AF: 0.0750

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

GnomAD4 genome AF: 0.0614 AC: 9345 AN: 152298 Hom.: 428 Cov.: 35 AF XY: 0.0586 AC XY: 4365 AN XY: 74458

African (AFR) AF: 0.0173 AC: 720 AN: 41554

American (AMR) AF: 0.0662 AC: 1013 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 400 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5190

South Asian (SAS) AF: 0.0377 AC: 182 AN: 4824

European-Finnish (FIN) AF: 0.0335 AC: 355 AN: 10606

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.0939 AC: 6389 AN: 68026

Other (OTH) AF: 0.0738 AC: 156 AN: 2114

Alfa AF: 0.0768 Hom.: 509

Bravo AF: 0.0628

Asia WGS AF: 0.0190 AC: 68 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	6.7
DANN	Benign	0.52
PhyloP100		0.99
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: rs17466478; hg19: chr3-11050518;