rs6778281

Variant names:

• chr3-11011831-C-A
• rs6778281
• NM_003042.4:c.-215-3841C>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003042.4(SLC6A1):​c.-215-3841C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.117 in 151,986 control chromosomes in the GnomAD database, including 1,517 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 0.12 (1517 hom., cov: 32)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0340
• Publications: 10 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-AS1 (HGNC:40546): (SLC6A1 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.238 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC6A1	NM_003042.4	c.-215-3841C>A		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.-215-3841C>A		intron_variant	Intron 1 of 15	1	NM_003042.4	ENSP00000287766.4

Frequencies

GnomAD3 genomes AF: 0.117 AC: 17734 AN: 151864 Hom.: 1514 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0143

Gnomad AMR AF: 0.0790

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.0894

Gnomad SAS AF: 0.0581

Gnomad FIN AF: 0.0292

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0708

Gnomad OTH AF: 0.106

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.117 AC: 17769 AN: 151982 Hom.: 1517 Cov.: 32 AF XY: 0.113 AC XY: 8428 AN XY: 74308

African (AFR) AF: 0.242 AC: 9996 AN: 41378

American (AMR) AF: 0.0792 AC: 1210 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 432 AN: 3470

East Asian (EAS) AF: 0.0896 AC: 463 AN: 5166

South Asian (SAS) AF: 0.0590 AC: 284 AN: 4814

European-Finnish (FIN) AF: 0.0292 AC: 309 AN: 10586

Middle Eastern (MID) AF: 0.0986 AC: 29 AN: 294

European-Non Finnish (NFE) AF: 0.0708 AC: 4813 AN: 67976

Other (OTH) AF: 0.104 AC: 220 AN: 2108

Alfa AF: 0.0908 Hom.: 2597

Bravo AF: 0.128

Asia WGS AF: 0.0850 AC: 294 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	1.8
DANN	Benign	0.68
PhyloP100		0.034
PromoterAI		0.023	Neutral
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: rs6778281; hg19: chr3-11053517;