3-11017195-C-T

Variant names:

• chr3-11017195-C-T
• rs41362845
• NM_003042.4:c.-17C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_003042.4(SLC6A1):​c.-17C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00122 in 1,609,842 control chromosomes in the GnomAD database, including 23 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0021 (7 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (16 hom.)
• Consequence: SLC6A1 NM_003042.4 5_prime_UTR
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.690
• Publications: 3 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 3-11017195-C-T is Benign according to our data. Variant chr3-11017195-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 1217800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.00211 (322/152314) while in subpopulation NFE AF = 0.000661 (45/68032). AF 95% confidence interval is 0.000508. There are 7 homozygotes in GnomAd4. There are 221 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 322 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.-17C>T		5_prime_UTR	Exon 3 of 16	NP_003033.3
	SLC6A1	NM_001348250.2		c.-17C>T		5_prime_UTR	Exon 3 of 16	NP_001335179.1	P30531
	SLC6A1	NM_001348251.2		c.-187C>T		5_prime_UTR	Exon 3 of 16	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.-17C>T		5_prime_UTR	Exon 3 of 16	ENSP00000287766.4	P30531
	SLC6A1	ENST00000698198.1		c.56C>T	p.Ala19Val	missense	Exon 1 of 14	ENSP00000513602.1	A0A8V8TMZ9
	SLC6A1	ENST00000644803.1		c.-17C>T		5_prime_UTR	Exon 1 of 14	ENSP00000494469.1	A0A2R8YDD5

Frequencies

GnomAD3 genomes AF: 0.00212 AC: 322 AN: 152196 Hom.: 7 Cov.: 32

Gnomad AFR AF: 0.000121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0252

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000661

Gnomad OTH AF: 0.00144

GnomAD2 exomes AF: 0.00252 AC: 629 AN: 249748 AF XY: 0.00235

Gnomad AFR exome AF: 0.000125

Gnomad AMR exome AF: 0.0000580

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0237

Gnomad NFE exome AF: 0.000896

Gnomad OTH exome AF: 0.00230

GnomAD4 exome AF: 0.00113 AC: 1649 AN: 1457528 Hom.: 16 Cov.: 30 AF XY: 0.00110 AC XY: 794 AN XY: 725060

African (AFR) AF: 0.000389 AC: 13 AN: 33404

American (AMR) AF: 0.000112 AC: 5 AN: 44706

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26088

East Asian (EAS) AF: 0.00 AC: 0 AN: 39670

South Asian (SAS) AF: 0.0000580 AC: 5 AN: 86134

European-Finnish (FIN) AF: 0.0228 AC: 1211 AN: 53124

Middle Eastern (MID) AF: 0.00481 AC: 27 AN: 5608

European-Non Finnish (NFE) AF: 0.000301 AC: 334 AN: 1108546

Other (OTH) AF: 0.000896 AC: 54 AN: 60248

GnomAD4 genome AF: 0.00211 AC: 322 AN: 152314 Hom.: 7 Cov.: 32 AF XY: 0.00297 AC XY: 221 AN XY: 74462

African (AFR) AF: 0.000120 AC: 5 AN: 41578

American (AMR) AF: 0.0000654 AC: 1 AN: 15302

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.0252 AC: 267 AN: 10616

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

European-Non Finnish (NFE) AF: 0.000661 AC: 45 AN: 68032

Other (OTH) AF: 0.00142 AC: 3 AN: 2108

Alfa AF: 0.00117 Hom.: 0

Bravo AF: 0.000283

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	12
DANN	Benign	0.91
PhyloP100		0.69
PromoterAI		-0.011	Neutral
Mutation Taster		=256/44	polymorphism

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: rs41362845; hg19: chr3-11058881; COSMIC: COSV55115832; COSMIC: COSV55115832;