3-11028856-GCC-GC

Variant names:

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

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+17delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0782 in 1,570,694 control chromosomes in the GnomAD database, including 13,253 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.17 (4554 hom., cov: 29)
  • Exomes 𝑓: 0.068 (8699 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-GC-G is Benign according to our data. Variant chr3-11028856-GC-G is described in ClinVar as Benign. ClinVar VariationId is 1166941.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.433 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+17delC		intron	N/A	NP_003033.3
	SLC6A1	NM_001348250.2		c.1191+17delC		intron	N/A	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.831+17delC		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+17delC		intron	N/A	ENSP00000287766.4	P30531
	SLC6A1	ENST00000698198.1		c.1263+17delC		intron	N/A	ENSP00000513602.1	A0A8V8TMZ9
	SLC6A1	ENST00000644803.1		c.1191+17delC		intron	N/A	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25520 AN: 151088 Hom.: 4527 Cov.: 29

Gnomad AFR AF: 0.437

Gnomad AMI AF: 0.134

Gnomad AMR AF: 0.0874

Gnomad ASJ AF: 0.0914

Gnomad EAS AF: 0.357

Gnomad SAS AF: 0.161

Gnomad FIN AF: 0.0224

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0389

Gnomad OTH AF: 0.142

GnomAD2 exomes AF: 0.113 AC: 26470 AN: 234778 AF XY: 0.109

Gnomad AFR exome AF: 0.458

Gnomad AMR exome AF: 0.0483

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.357

Gnomad FIN exome AF: 0.0281

Gnomad NFE exome AF: 0.0432

Gnomad OTH exome AF: 0.0809

GnomAD4 exome AF: 0.0685 AC: 97230 AN: 1419488 Hom.: 8699 Cov.: 24 AF XY: 0.0699 AC XY: 49530 AN XY: 708456

African (AFR) AF: 0.460 AC: 14834 AN: 32276

American (AMR) AF: 0.0494 AC: 2193 AN: 44430

Ashkenazi Jewish (ASJ) AF: 0.0947 AC: 2446 AN: 25824

East Asian (EAS) AF: 0.338 AC: 13325 AN: 39406

South Asian (SAS) AF: 0.157 AC: 13376 AN: 84970

European-Finnish (FIN) AF: 0.0278 AC: 1473 AN: 52958

Middle Eastern (MID) AF: 0.107 AC: 594 AN: 5552

European-Non Finnish (NFE) AF: 0.0398 AC: 42824 AN: 1075174

Other (OTH) AF: 0.105 AC: 6165 AN: 58898

GnomAD4 genome AF: 0.169 AC: 25610 AN: 151206 Hom.: 4554 Cov.: 29 AF XY: 0.170 AC XY: 12526 AN XY: 73838

African (AFR) AF: 0.438 AC: 18041 AN: 41184

American (AMR) AF: 0.0872 AC: 1324 AN: 15180

Ashkenazi Jewish (ASJ) AF: 0.0914 AC: 316 AN: 3456

East Asian (EAS) AF: 0.357 AC: 1824 AN: 5110

South Asian (SAS) AF: 0.162 AC: 772 AN: 4774

European-Finnish (FIN) AF: 0.0224 AC: 234 AN: 10450

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.0389 AC: 2639 AN: 67758

Other (OTH) AF: 0.147 AC: 308 AN: 2090

Alfa AF: 0.0400 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;