rs142579600

Variant names:

• chr3-11018704-T-C
• rs142579600
• NM_003042.4:c.471+6T>C

Variant summary

Our verdict is Benign. The variant received -18 ACMG points: 0P and 18B. BP4_Moderate BP6_Very_Strong BS1 BS2

The NM_003042.4(SLC6A1):​c.471+6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00029 in 1,557,944 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0015 (1 hom., cov: 33)
  • Exomes 𝑓: 0.00016 (0 hom.)
• Consequence: SLC6A1 NM_003042.4 splice_region, intron
• Scores: Splicing: ADA: 0.006254
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.979
• Publications: 0 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 -18 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.42).
• BP6: Variant 3-11018704-T-C is Benign according to our data. Variant chr3-11018704-T-C is described in ClinVar as Benign. ClinVar VariationId is 475482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00146 (222/152090) while in subpopulation AFR AF = 0.00528 (219/41474). AF 95% confidence interval is 0.00471. There are 1 homozygotes in GnomAd4. There are 114 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 222 AD,Unknown gene.

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.471+6T>C		splice_region intron	N/A	NP_003033.3
	SLC6A1	NM_001348250.2		c.471+6T>C		splice_region intron	N/A	NP_001335179.1
	SLC6A1	NM_001348251.2		c.111+6T>C		splice_region intron	N/A	NP_001335180.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC6A1	ENST00000287766.10	TSL:1 MANE Select	c.471+6T>C		splice_region intron	N/A	ENSP00000287766.4
	SLC6A1	ENST00000644175.1		c.477T>C	p.Ser159Ser	synonymous	Exon 4 of 4	ENSP00000493788.1
	SLC6A1	ENST00000646088.1		c.477T>C	p.Ser159Ser	synonymous	Exon 5 of 5	ENSP00000494608.1

Frequencies

GnomAD3 genomes AF: 0.00143 AC: 217 AN: 151972 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.00518

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.000383 AC: 96 AN: 250960 AF XY: 0.000214

Gnomad AFR exome AF: 0.00567

Gnomad AMR exome AF: 0.0000579

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.000164

GnomAD4 exome AF: 0.000164 AC: 230 AN: 1405854 Hom.: 0 Cov.: 24 AF XY: 0.000131 AC XY: 92 AN XY: 702882

African (AFR) AF: 0.00606 AC: 196 AN: 32354

American (AMR) AF: 0.000134 AC: 6 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25804

East Asian (EAS) AF: 0.00 AC: 0 AN: 39432

South Asian (SAS) AF: 0.0000470 AC: 4 AN: 85076

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53382

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5674

European-Non Finnish (NFE) AF: 9.43e-7 AC: 1 AN: 1060948

Other (OTH) AF: 0.000376 AC: 22 AN: 58518

GnomAD4 genome AF: 0.00146 AC: 222 AN: 152090 Hom.: 1 Cov.: 33 AF XY: 0.00153 AC XY: 114 AN XY: 74352

African (AFR) AF: 0.00528 AC: 219 AN: 41474

American (AMR) AF: 0.00 AC: 0 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5154

South Asian (SAS) AF: 0.000208 AC: 1 AN: 4818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 67986

Other (OTH) AF: 0.000475 AC: 1 AN: 2104

Alfa AF: 0.000818 Hom.: 0

Bravo AF: 0.00160

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Epilepsy with myoclonic atonic seizures (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.42
CADD	Benign	4.2
DANN	Benign	0.87
PhyloP100		0.98

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0063
dbscSNV1_RF	Benign	0.084
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: rs142579600; hg19: chr3-11060390;