ENST00000598504.5:c.-461G>A

Variant names:

• chr19-14977214-C-T
• rs1548543
• ENST00000598504.5:c.-461G>A

Variant summary

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

The ENST00000598504.5(SLC1A6):​c.-461G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.682 in 151,758 control chromosomes in the GnomAD database, including 35,316 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 0.68 (35316 hom., cov: 30)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: SLC1A6 ENST00000598504.5 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361
• Publications: 4 publications found

Genes affected

SLC1A6 (HGNC:10944): (solute carrier family 1 member 6) Predicted to enable high-affinity glutamate transmembrane transporter activity. Involved in neurotransmitter uptake. Located in intermediate filament cytoskeleton and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC1A6	NM_005071.3	c.-8+2095G>A		intron_variant	Intron 1 of 9	ENST00000594383.2	NP_005062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC1A6	ENST00000594383.2	c.-8+2095G>A		intron_variant	Intron 1 of 9	2	NM_005071.3	ENSP00000472133.2

Frequencies

GnomAD3 genomes AF: 0.682 AC: 103368 AN: 151636 Hom.: 35292 Cov.: 30

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.714

Gnomad AMR AF: 0.658

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.692

Gnomad SAS AF: 0.718

Gnomad FIN AF: 0.707

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.668

Gnomad OTH AF: 0.656

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 2 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.682 AC: 103437 AN: 151754 Hom.: 35316 Cov.: 30 AF XY: 0.685 AC XY: 50771 AN XY: 74116

African (AFR) AF: 0.717 AC: 29686 AN: 41380

American (AMR) AF: 0.657 AC: 10002 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1764 AN: 3464

East Asian (EAS) AF: 0.691 AC: 3551 AN: 5136

South Asian (SAS) AF: 0.719 AC: 3445 AN: 4792

European-Finnish (FIN) AF: 0.707 AC: 7413 AN: 10490

Middle Eastern (MID) AF: 0.605 AC: 178 AN: 294

European-Non Finnish (NFE) AF: 0.668 AC: 45372 AN: 67954

Other (OTH) AF: 0.652 AC: 1376 AN: 2112

Alfa AF: 0.669 Hom.: 27151

Bravo AF: 0.677

Asia WGS AF: 0.699 AC: 2430 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	5.0
DANN	Benign	0.67
PhyloP100		0.36
PromoterAI		-0.015	Neutral
Mutation Taster		=300/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1548543; hg19: chr19-15088026;