rs2675163

Variant names:

• chr3-11033328-C-T
• rs2675163
• NM_003042.4:c.1427-311C>T

Your query was ambiguous. Multiple possible variants found:

• chr3-11033328-C-T
• chr3-11033328-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003042.4(SLC6A1):​c.1427-311C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.78 in 202,882 control chromosomes in the GnomAD database, including 62,050 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (47338 hom., cov: 33)
  • Exomes 𝑓: 0.76 (14712 hom.)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.933
• Publications: 8 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, Labcorp Genetics (formerly Invitae), PanelApp Australia, Illumina, G2P
• myoclonic-astatic epilepsy

  Inheritance: Unknown Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BP6: Variant 3-11033328-C-T is Benign according to our data. Variant chr3-11033328-C-T is described in ClinVar as Benign. ClinVar VariationId is 1248256.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.851 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.1427-311C>T		intron	N/A	NP_003033.3
	SLC6A1	NM_001348250.2		c.1427-311C>T		intron	N/A	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.1067-311C>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.1427-311C>T		intron	N/A	ENSP00000287766.4	P30531
	SLC6A1	ENST00000698198.1		c.1499-311C>T		intron	N/A	ENSP00000513602.1	A0A8V8TMZ9
	SLC6A1	ENST00000644803.1		c.1454-311C>T		intron	N/A	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes AF: 0.787 AC: 119698 AN: 152082 Hom.: 47294 Cov.: 33

Gnomad AFR AF: 0.858

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.755

Gnomad ASJ AF: 0.785

Gnomad EAS AF: 0.642

Gnomad SAS AF: 0.717

Gnomad FIN AF: 0.767

Gnomad MID AF: 0.728

Gnomad NFE AF: 0.772

Gnomad OTH AF: 0.788

GnomAD4 exome AF: 0.758 AC: 38392 AN: 50682 Hom.: 14712 Cov.: 0 AF XY: 0.757 AC XY: 19641 AN XY: 25956

African (AFR) AF: 0.852 AC: 1915 AN: 2248

American (AMR) AF: 0.746 AC: 1691 AN: 2268

Ashkenazi Jewish (ASJ) AF: 0.776 AC: 1675 AN: 2158

East Asian (EAS) AF: 0.636 AC: 2404 AN: 3782

South Asian (SAS) AF: 0.694 AC: 1038 AN: 1496

European-Finnish (FIN) AF: 0.759 AC: 1982 AN: 2610

Middle Eastern (MID) AF: 0.719 AC: 187 AN: 260

European-Non Finnish (NFE) AF: 0.769 AC: 24932 AN: 32430

Other (OTH) AF: 0.749 AC: 2568 AN: 3430

GnomAD4 genome AF: 0.787 AC: 119799 AN: 152200 Hom.: 47338 Cov.: 33 AF XY: 0.784 AC XY: 58347 AN XY: 74392

African (AFR) AF: 0.858 AC: 35644 AN: 41532

American (AMR) AF: 0.755 AC: 11544 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.785 AC: 2724 AN: 3472

East Asian (EAS) AF: 0.642 AC: 3316 AN: 5168

South Asian (SAS) AF: 0.718 AC: 3466 AN: 4830

European-Finnish (FIN) AF: 0.767 AC: 8115 AN: 10582

Middle Eastern (MID) AF: 0.731 AC: 215 AN: 294

European-Non Finnish (NFE) AF: 0.772 AC: 52505 AN: 68002

Other (OTH) AF: 0.784 AC: 1655 AN: 2112

Alfa AF: 0.775 Hom.: 79015

Bravo AF: 0.789

Asia WGS AF: 0.720 AC: 2506 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.70
DANN	Benign	0.54
PhyloP100		-0.93
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: rs2675163; hg19: chr3-11075014;