chr3-11016816-T-C

Variant names:

• chr3-11016816-T-C
• rs11923810
• NM_003042.4:c.-153-243T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_003042.4(SLC6A1):​c.-153-243T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.088 in 152,188 control chromosomes in the GnomAD database, including 1,564 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.088 (1564 hom., cov: 32)
• Consequence: SLC6A1 NM_003042.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.562
• 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-AS1 (HGNC:40546): (SLC6A1 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 3-11016816-T-C is Benign according to our data. Variant chr3-11016816-T-C is described in ClinVar as Benign. ClinVar VariationId is 1288263.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.264 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.-153-243T>C		intron	N/A	NP_003033.3
	SLC6A1	NM_001348250.2		c.-92-304T>C		intron	N/A	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.-262-304T>C		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.-153-243T>C		intron	N/A	ENSP00000287766.4	P30531
	SLC6A1	ENST00000642201.1		c.-25-371T>C		intron	N/A	ENSP00000494778.1	P30531
	SLC6A1	ENST00000642515.1		c.-153-243T>C		intron	N/A	ENSP00000496348.1	P30531

Frequencies

GnomAD3 genomes AF: 0.0878 AC: 13355 AN: 152070 Hom.: 1557 Cov.: 32

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0467

Gnomad ASJ AF: 0.0433

Gnomad EAS AF: 0.0893

Gnomad SAS AF: 0.0469

Gnomad FIN AF: 0.00104

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00813

Gnomad OTH AF: 0.0645

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0880 AC: 13394 AN: 152188 Hom.: 1564 Cov.: 32 AF XY: 0.0864 AC XY: 6429 AN XY: 74396

African (AFR) AF: 0.268 AC: 11123 AN: 41474

American (AMR) AF: 0.0469 AC: 717 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0433 AC: 150 AN: 3468

East Asian (EAS) AF: 0.0896 AC: 463 AN: 5170

South Asian (SAS) AF: 0.0471 AC: 227 AN: 4816

European-Finnish (FIN) AF: 0.00104 AC: 11 AN: 10614

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.00813 AC: 553 AN: 68022

Other (OTH) AF: 0.0633 AC: 134 AN: 2116

Alfa AF: 0.0404 Hom.: 138

Bravo AF: 0.100

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.6
DANN	Benign	0.65
PhyloP100		0.56
PromoterAI		0.045	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: rs11923810; hg19: chr3-11058502;