17-7283804-T-C

Variant names:

• chr17-7283804-T-C
• rs5435
• NM_001042.3:c.390T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001042.3(SLC2A4):​c.390T>C​(p.Asn130Asn) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,613,772 control chromosomes in the GnomAD database, including 329,905 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 0.70 (37714 hom., cov: 32)
  • Exomes 𝑓: 0.63 (292191 hom.)
• Consequence: SLC2A4 NM_001042.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.48
• Publications: 48 publications found

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]

ENSG00000263342 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.06).
• BP7: Synonymous conserved (PhyloP=-3.48 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.846 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042.3. 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
	SLC2A4	NM_001042.3	MANE Select	c.390T>C	p.Asn130Asn	synonymous	Exon 4 of 11	NP_001033.1	P14672-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A4	ENST00000317370.13	TSL:1 MANE Select	c.390T>C	p.Asn130Asn	synonymous	Exon 4 of 11	ENSP00000320935.8	P14672-1
	SLC2A4	ENST00000572485.5	TSL:1	n.390T>C		non_coding_transcript_exon	Exon 4 of 11	ENSP00000461086.1	P14672-2
	SLC2A4	ENST00000954706.1		c.390T>C	p.Asn130Asn	synonymous	Exon 4 of 11	ENSP00000624765.1

Frequencies

GnomAD3 genomes AF: 0.696 AC: 105825 AN: 151940 Hom.: 37644 Cov.: 32

Gnomad AFR AF: 0.853

Gnomad AMI AF: 0.584

Gnomad AMR AF: 0.664

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.648

Gnomad SAS AF: 0.652

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.788

Gnomad NFE AF: 0.628

Gnomad OTH AF: 0.708

GnomAD2 exomes AF: 0.647 AC: 162129 AN: 250728 AF XY: 0.646

Gnomad AFR exome AF: 0.858

Gnomad AMR exome AF: 0.595

Gnomad ASJ exome AF: 0.636

Gnomad EAS exome AF: 0.643

Gnomad FIN exome AF: 0.627

Gnomad NFE exome AF: 0.634

Gnomad OTH exome AF: 0.648

GnomAD4 exome AF: 0.630 AC: 921529 AN: 1461714 Hom.: 292191 Cov.: 59 AF XY: 0.631 AC XY: 459101 AN XY: 727158

African (AFR) AF: 0.863 AC: 28880 AN: 33480

American (AMR) AF: 0.605 AC: 27063 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 16842 AN: 26136

East Asian (EAS) AF: 0.639 AC: 25358 AN: 39698

South Asian (SAS) AF: 0.653 AC: 56333 AN: 86256

European-Finnish (FIN) AF: 0.624 AC: 33258 AN: 53330

Middle Eastern (MID) AF: 0.738 AC: 4255 AN: 5768

European-Non Finnish (NFE) AF: 0.621 AC: 690551 AN: 1111940

Other (OTH) AF: 0.646 AC: 38989 AN: 60390

GnomAD4 genome AF: 0.697 AC: 105960 AN: 152058 Hom.: 37714 Cov.: 32 AF XY: 0.696 AC XY: 51772 AN XY: 74336

African (AFR) AF: 0.854 AC: 35451 AN: 41522

American (AMR) AF: 0.664 AC: 10152 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2200 AN: 3470

East Asian (EAS) AF: 0.647 AC: 3333 AN: 5148

South Asian (SAS) AF: 0.653 AC: 3152 AN: 4824

European-Finnish (FIN) AF: 0.640 AC: 6772 AN: 10576

Middle Eastern (MID) AF: 0.789 AC: 232 AN: 294

European-Non Finnish (NFE) AF: 0.628 AC: 42638 AN: 67924

Other (OTH) AF: 0.712 AC: 1500 AN: 2108

Alfa AF: 0.644 Hom.: 55591

Bravo AF: 0.704

Asia WGS AF: 0.687 AC: 2391 AN: 3478

EpiCase AF: 0.648

EpiControl AF: 0.649

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.1
CADD	Benign	0.027
DANN	Benign	0.45
PhyloP100		-3.5
Mutation Taster		=99/1	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: rs5435; hg19: chr17-7187123; COSMIC: COSV50300952; COSMIC: COSV50300952;