rs2097837

Positions:

• chr19-14968175-G-A
• chr19-14968175-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005071.3(SLC1A6):​c.548+128C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.325 in 743,050 control chromosomes in the GnomAD database, including 40,781 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 0.34 (8695 hom., cov: 31)
  • Exomes 𝑓: 0.32 (32086 hom.)
• Consequence: SLC1A6 NM_005071.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.10

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.37 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC1A6	NM_005071.3	c.548+128C>T		intron_variant		ENST00000594383.2	NP_005062.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC1A6	ENST00000594383.2	c.548+128C>T		intron_variant		2	NM_005071.3	ENSP00000472133	P1

Frequencies

GnomAD3 genomes AF: 0.335 AC: 50857 AN: 151626 Hom.: 8684 Cov.: 31

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.320

Gnomad AMR AF: 0.306

Gnomad ASJ AF: 0.288

Gnomad EAS AF: 0.110

Gnomad SAS AF: 0.337

Gnomad FIN AF: 0.315

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.322

GnomAD4 exome AF: 0.322 AC: 190497 AN: 591308 Hom.: 32086 AF XY: 0.323 AC XY: 98371 AN XY: 304324

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.296

Gnomad4 ASJ exome AF: 0.298

Gnomad4 EAS exome AF: 0.0943

Gnomad4 SAS exome AF: 0.341

Gnomad4 FIN exome AF: 0.312

Gnomad4 NFE exome AF: 0.339

Gnomad4 OTH exome AF: 0.322

GnomAD4 genome AF: 0.335 AC: 50906 AN: 151742 Hom.: 8695 Cov.: 31 AF XY: 0.332 AC XY: 24595 AN XY: 74146

Gnomad4 AFR AF: 0.375

Gnomad4 AMR AF: 0.306

Gnomad4 ASJ AF: 0.288

Gnomad4 EAS AF: 0.111

Gnomad4 SAS AF: 0.339

Gnomad4 FIN AF: 0.315

Gnomad4 NFE AF: 0.341

Gnomad4 OTH AF: 0.320

Alfa AF: 0.341 Hom.: 2127

Bravo AF: 0.333

Asia WGS AF: 0.242 AC: 841 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	5.7
DANN	Benign	0.45

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

Publications

LitVar

Other links and lift over

dbSNP: rs2097837; hg19: chr19-15078987;