3-11007447-C-T

Variant names:

• chr3-11007447-C-T
• rs1710891
• NM_003042.4:c.-215-8225C>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.-215-8225C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 152,178 control chromosomes in the GnomAD database, including 11,433 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 0.38 (11422 hom., cov: 33)
  • Exomes 𝑓: 0.51 (11 hom.)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361
• Publications: 4 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=-0.96).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.448 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.-215-8225C>T		intron	N/A	NP_003033.3
	SLC6A1	NM_001348250.2		c.-154-8225C>T		intron	N/A	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.-324-8225C>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.-215-8225C>T		intron	N/A	ENSP00000287766.4	P30531
	SLC6A1	ENST00000642201.1		c.-25-9740C>T		intron	N/A	ENSP00000494778.1	P30531
	SLC6A1	ENST00000642515.1		c.-1222-5152C>T		intron	N/A	ENSP00000496348.1	P30531

Frequencies

GnomAD3 genomes AF: 0.384 AC: 58308 AN: 151980 Hom.: 11411 Cov.: 33

Gnomad AFR AF: 0.404

Gnomad AMI AF: 0.422

Gnomad AMR AF: 0.296

Gnomad ASJ AF: 0.381

Gnomad EAS AF: 0.464

Gnomad SAS AF: 0.393

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.387

Gnomad OTH AF: 0.387

GnomAD4 exome AF: 0.512 AC: 41 AN: 80 Hom.: 11 AF XY: 0.441 AC XY: 30 AN XY: 68

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

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

Middle Eastern (MID) AF: 0.500 AC: 1 AN: 2

European-Non Finnish (NFE) AF: 0.485 AC: 33 AN: 68

Other (OTH) AF: 0.500 AC: 2 AN: 4

GnomAD4 genome AF: 0.384 AC: 58355 AN: 152098 Hom.: 11422 Cov.: 33 AF XY: 0.383 AC XY: 28443 AN XY: 74346

African (AFR) AF: 0.404 AC: 16764 AN: 41486

American (AMR) AF: 0.296 AC: 4521 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.381 AC: 1320 AN: 3468

East Asian (EAS) AF: 0.463 AC: 2391 AN: 5160

South Asian (SAS) AF: 0.392 AC: 1891 AN: 4824

European-Finnish (FIN) AF: 0.365 AC: 3857 AN: 10560

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.387 AC: 26310 AN: 67994

Other (OTH) AF: 0.388 AC: 820 AN: 2112

Alfa AF: 0.387 Hom.: 23855

Bravo AF: 0.378

Asia WGS AF: 0.410 AC: 1425 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.64
DANN	Benign	0.53
PhyloP100		-0.36
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: rs1710891; hg19: chr3-11049133;