rs5417

Positions:

• chr17-7281743-C-A
• chr17-7281743-C-T

Variant summary

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

The NM_001042.3(SLC2A4):​c.-192C>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 0.545 in 644,948 control chromosomes in the GnomAD database, including 99,019 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 0.49 (19809 hom., cov: 33)
  • Exomes 𝑓: 0.56 (79210 hom.)
• Consequence: SLC2A4 NM_001042.3 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.349

Genes affected

SLC2A4 (HGNC:11009): (solute carrier family 2 member 4) This gene is a member of the solute carrier family 2 (facilitated glucose transporter) family and encodes a protein that functions as an insulin-regulated facilitative glucose transporter. In the absence of insulin, this integral membrane protein is sequestered within the cells of muscle and adipose tissue. Within minutes of insulin stimulation, the protein moves to the cell surface and begins to transport glucose across the cell membrane. Mutations in this gene have been associated with noninsulin-dependent diabetes mellitus (NIDDM). [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.579 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A4	NM_001042.3	c.-192C>A		5_prime_UTR_variant	1/11	ENST00000317370.13	NP_001033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A4	ENST00000317370.13	c.-192C>A		5_prime_UTR_variant	1/11	1	NM_001042.3	ENSP00000320935	P1
SLC2A4	ENST00000572485.5	c.-192C>A		5_prime_UTR_variant, NMD_transcript_variant	1/11	1		ENSP00000461086
SLC2A4	ENST00000571308.5	c.-192C>A		5_prime_UTR_variant	1/10	5		ENSP00000459864

Frequencies

GnomAD3 genomes AF: 0.493 AC: 74856 AN: 151970 Hom.: 19791 Cov.: 33

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.549

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.591

Gnomad EAS AF: 0.376

Gnomad SAS AF: 0.560

Gnomad FIN AF: 0.622

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.584

Gnomad OTH AF: 0.540

GnomAD4 exome AF: 0.561 AC: 276289 AN: 492860 Hom.: 79210 Cov.: 5 AF XY: 0.564 AC XY: 147213 AN XY: 260912

Gnomad4 AFR exome AF: 0.284

Gnomad4 AMR exome AF: 0.490

Gnomad4 ASJ exome AF: 0.600

Gnomad4 EAS exome AF: 0.363

Gnomad4 SAS exome AF: 0.575

Gnomad4 FIN exome AF: 0.610

Gnomad4 NFE exome AF: 0.590

Gnomad4 OTH exome AF: 0.547

GnomAD4 genome AF: 0.493 AC: 74913 AN: 152088 Hom.: 19809 Cov.: 33 AF XY: 0.497 AC XY: 36953 AN XY: 74362

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.526

Gnomad4 ASJ AF: 0.591

Gnomad4 EAS AF: 0.376

Gnomad4 SAS AF: 0.562

Gnomad4 FIN AF: 0.622

Gnomad4 NFE AF: 0.584

Gnomad4 OTH AF: 0.546

Alfa AF: 0.571 Hom.: 40087

Bravo AF: 0.473

Asia WGS AF: 0.481 AC: 1672 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
CADD	Benign	15
DANN	Benign	0.69

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: rs5417; hg19: chr17-7185062;