rs9990174

Variant names:

• chr3-10998753-G-T
• rs9990174
• NM_003042.4:c.-216+5824G>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.-216+5824G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,086 control chromosomes in the GnomAD database, including 7,736 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 0.31 (7736 hom., cov: 32)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750
• Publications: 14 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 Gene-Disease associations (from GenCC):

• epilepsy with myoclonic atonic seizures

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Illumina, G2P, Labcorp Genetics (formerly Invitae)
• myoclonic-astatic epilepsy

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4	c.-216+5824G>T		intron_variant	Intron 1 of 15	ENST00000287766.10	NP_003033.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC6A1	ENST00000287766.10	c.-216+5824G>T		intron_variant	Intron 1 of 15	1	NM_003042.4	ENSP00000287766.4

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47045 AN: 151968 Hom.: 7728 Cov.: 32

Gnomad AFR AF: 0.209

Gnomad AMI AF: 0.280

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.301

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.386

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.337

Gnomad OTH AF: 0.325

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

GnomAD4 genome AF: 0.310 AC: 47073 AN: 152086 Hom.: 7736 Cov.: 32 AF XY: 0.312 AC XY: 23189 AN XY: 74314

African (AFR) AF: 0.209 AC: 8686 AN: 41510

American (AMR) AF: 0.429 AC: 6551 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.301 AC: 1044 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1280 AN: 5158

South Asian (SAS) AF: 0.386 AC: 1860 AN: 4816

European-Finnish (FIN) AF: 0.350 AC: 3696 AN: 10556

Middle Eastern (MID) AF: 0.323 AC: 95 AN: 294

European-Non Finnish (NFE) AF: 0.337 AC: 22914 AN: 67970

Other (OTH) AF: 0.327 AC: 692 AN: 2114

Alfa AF: 0.329 Hom.: 30241

Bravo AF: 0.312

Asia WGS AF: 0.307 AC: 1068 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.70
PhyloP100		0.075
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: rs9990174; hg19: chr3-11040439;