3-11028856-GCC-GCCC

Variant names:

• chr3-11028856-G-GC
• rs3841958
• NM_003042.4:c.1191+17dupC

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003042.4(SLC6A1):​c.1191+17dupC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00717 in 1,570,444 control chromosomes in the GnomAD database, including 313 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.028 (183 hom., cov: 29)
  • Exomes 𝑓: 0.0050 (130 hom.)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.92
• Publications: 1 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 -16 ACMG points.

• BP6: Variant 3-11028856-G-GC is Benign according to our data. Variant chr3-11028856-G-GC is described in ClinVar as Benign. ClinVar VariationId is 475468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0894 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.1191+17dupC		intron	N/A	NP_003033.3
	SLC6A1	NM_001348250.2		c.1191+17dupC		intron	N/A	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.831+17dupC		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.1191+17dupC		intron	N/A	ENSP00000287766.4	P30531
	SLC6A1	ENST00000698198.1		c.1263+17dupC		intron	N/A	ENSP00000513602.1	A0A8V8TMZ9
	SLC6A1	ENST00000644803.1		c.1191+17dupC		intron	N/A	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes AF: 0.0277 AC: 4180 AN: 151116 Hom.: 183 Cov.: 29

Gnomad AFR AF: 0.0920

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0111

Gnomad ASJ AF: 0.000578

Gnomad EAS AF: 0.00156

Gnomad SAS AF: 0.00293

Gnomad FIN AF: 0.000287

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.00245

Gnomad OTH AF: 0.0174

GnomAD2 exomes AF: 0.00906 AC: 2128 AN: 234778 AF XY: 0.00679

Gnomad AFR exome AF: 0.0872

Gnomad AMR exome AF: 0.00769

Gnomad ASJ exome AF: 0.00148

Gnomad EAS exome AF: 0.00107

Gnomad FIN exome AF: 0.000701

Gnomad NFE exome AF: 0.00353

Gnomad OTH exome AF: 0.00576

GnomAD4 exome AF: 0.00499 AC: 7082 AN: 1419210 Hom.: 130 Cov.: 24 AF XY: 0.00454 AC XY: 3215 AN XY: 708432

African (AFR) AF: 0.0863 AC: 2785 AN: 32262

American (AMR) AF: 0.00808 AC: 359 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.000348 AC: 9 AN: 25826

East Asian (EAS) AF: 0.00127 AC: 50 AN: 39410

South Asian (SAS) AF: 0.00204 AC: 173 AN: 85012

European-Finnish (FIN) AF: 0.00314 AC: 165 AN: 52602

Middle Eastern (MID) AF: 0.00486 AC: 27 AN: 5554

European-Non Finnish (NFE) AF: 0.00287 AC: 3083 AN: 1075196

Other (OTH) AF: 0.00732 AC: 431 AN: 58906

GnomAD4 genome AF: 0.0277 AC: 4182 AN: 151234 Hom.: 183 Cov.: 29 AF XY: 0.0260 AC XY: 1922 AN XY: 73858

African (AFR) AF: 0.0919 AC: 3784 AN: 41192

American (AMR) AF: 0.0110 AC: 167 AN: 15178

Ashkenazi Jewish (ASJ) AF: 0.000578 AC: 2 AN: 3458

East Asian (EAS) AF: 0.00156 AC: 8 AN: 5116

South Asian (SAS) AF: 0.00272 AC: 13 AN: 4776

European-Finnish (FIN) AF: 0.000287 AC: 3 AN: 10452

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00245 AC: 166 AN: 67768

Other (OTH) AF: 0.0172 AC: 36 AN: 2090

Alfa AF: 0.00323 Hom.: 63

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Epilepsy with myoclonic atonic seizures (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.9
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: rs3841958; hg19: chr3-11070542;