17-7284083-C-T

Variant names:

• chr17-7284083-C-T
• rs145632483
• NM_001042.3:c.558C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_001042.3(SLC2A4):​c.558C>T​(p.Ile186Ile) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000394 in 1,613,506 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0018 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00025 (1 hom.)
• Consequence: SLC2A4 NM_001042.3 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.11

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=-0.81).
• BP6: Variant 17-7284083-C-T is Benign according to our data. Variant chr17-7284083-C-T is described in ClinVar as [Benign]. Clinvar id is 713532.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.11 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A4	NM_001042.3	c.558C>T	p.Ile186Ile	synonymous_variant	Exon 5 of 11	ENST00000317370.13	NP_001033.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A4	ENST00000317370.13	c.558C>T	p.Ile186Ile	synonymous_variant	Exon 5 of 11	1	NM_001042.3	ENSP00000320935.8

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 269 AN: 152238 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00593

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000392

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000282

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00191

GnomAD2 exomes AF: 0.000557 AC: 139 AN: 249448 AF XY: 0.000437

Gnomad AFR exome AF: 0.00606

Gnomad AMR exome AF: 0.000407

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000186

Gnomad NFE exome AF: 0.000160

Gnomad OTH exome AF: 0.000821

GnomAD4 exome AF: 0.000250 AC: 366 AN: 1461150 Hom.: 1 Cov.: 34 AF XY: 0.000201 AC XY: 146 AN XY: 726832

Gnomad4 AFR exome AF: 0.00670 AC: 224 AN: 33456

Gnomad4 AMR exome AF: 0.000560 AC: 25 AN: 44648

Gnomad4 ASJ exome AF: 0.00 AC: 0 AN: 26114

Gnomad4 EAS exome AF: 0.00 AC: 0 AN: 39662

Gnomad4 SAS exome AF: 0.0000116 AC: 1 AN: 86152

Gnomad4 FIN exome AF: 0.000169 AC: 9 AN: 53310

Gnomad4 NFE exome AF: 0.0000432 AC: 48 AN: 1111680

Gnomad4 Remaining exome AF: 0.000795 AC: 48 AN: 60360

GnomAD4 genome AF: 0.00177 AC: 269 AN: 152356 Hom.: 1 Cov.: 32 AF XY: 0.00174 AC XY: 130 AN XY: 74500

Gnomad4 AFR AF: 0.00592 AC: 0.00591545 AN: 0.00591545

Gnomad4 AMR AF: 0.000392 AC: 0.000391952 AN: 0.000391952

Gnomad4 ASJ AF: 0.00 AC: 0 AN: 0

Gnomad4 EAS AF: 0.00 AC: 0 AN: 0

Gnomad4 SAS AF: 0.00 AC: 0 AN: 0

Gnomad4 FIN AF: 0.000282 AC: 0.000282326 AN: 0.000282326

Gnomad4 NFE AF: 0.000147 AC: 0.000147007 AN: 0.000147007

Gnomad4 OTH AF: 0.00189 AC: 0.00189036 AN: 0.00189036

Alfa AF: 0.000835 Hom.: 1

Bravo AF: 0.00180

Asia WGS AF: 0.000577 AC: 2 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

May 15, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.0
DANN	Benign	0.83
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs145632483; hg19: chr17-7187402;