NM_003042.4:c.-216+2009C>T

Variant names:

• chr3-10994938-C-T
• rs2601126
• NM_003042.4:c.-216+2009C>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+2009C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 151,970 control chromosomes in the GnomAD database, including 15,439 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 0.44 (15439 hom., cov: 32)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.404
• 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=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.57 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4	c.-216+2009C>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+2009C>T		intron_variant	Intron 1 of 15	1	NM_003042.4	ENSP00000287766.4

Frequencies

GnomAD3 genomes AF: 0.441 AC: 67006 AN: 151852 Hom.: 15420 Cov.: 32

Gnomad AFR AF: 0.575

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.409

Gnomad ASJ AF: 0.487

Gnomad EAS AF: 0.406

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.313

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.434

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

GnomAD4 genome AF: 0.441 AC: 67071 AN: 151970 Hom.: 15439 Cov.: 32 AF XY: 0.440 AC XY: 32720 AN XY: 74290

African (AFR) AF: 0.576 AC: 23848 AN: 41428

American (AMR) AF: 0.409 AC: 6245 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.487 AC: 1689 AN: 3466

East Asian (EAS) AF: 0.404 AC: 2085 AN: 5156

South Asian (SAS) AF: 0.563 AC: 2706 AN: 4810

European-Finnish (FIN) AF: 0.313 AC: 3310 AN: 10562

Middle Eastern (MID) AF: 0.473 AC: 139 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25744 AN: 67956

Other (OTH) AF: 0.433 AC: 912 AN: 2106

Alfa AF: 0.407 Hom.: 30866

Bravo AF: 0.451

Asia WGS AF: 0.475 AC: 1653 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	9.7
DANN	Benign	0.67
PhyloP100		0.40
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: rs2601126; hg19: chr3-11036624;