rs4475146

Variant names:

• chr4-9945032-C-A
• rs4475146
• NM_020041.3:c.682-2987G>T

Variant summary

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

The NM_020041.3(SLC2A9):​c.682-2987G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,156 control chromosomes in the GnomAD database, including 7,013 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 0.29 (7013 hom., cov: 33)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.582
• Publications: 19 publications found

Genes affected

SLC2A9 (HGNC:13446): (solute carrier family 2 member 9) This gene encodes a member of the SLC2A facilitative glucose transporter family. Members of this family play a significant role in maintaining glucose homeostasis. The encoded protein may play a role in the development and survival of chondrocytes in cartilage matrices. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

SLC2A9 Gene-Disease associations (from GenCC):

• hypouricemia, renal, 2

  Inheritance: AR, AD, SD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
• hereditary renal hypouricemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020041.3. 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
	SLC2A9	NM_020041.3	MANE Select	c.682-2987G>T		intron	N/A	NP_064425.2
	SLC2A9	NM_001001290.2		c.595-2987G>T		intron	N/A	NP_001001290.1	Q9NRM0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A9	ENST00000264784.8	TSL:1 MANE Select	c.682-2987G>T		intron	N/A	ENSP00000264784.3	Q9NRM0-1
	SLC2A9	ENST00000309065.7	TSL:1	c.595-2987G>T		intron	N/A	ENSP00000311383.3	Q9NRM0-2
	SLC2A9	ENST00000505104.5	TSL:1	n.716-2987G>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43373 AN: 152038 Hom.: 7000 Cov.: 33

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.361

Gnomad ASJ AF: 0.287

Gnomad EAS AF: 0.0199

Gnomad SAS AF: 0.247

Gnomad FIN AF: 0.201

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.270

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.285 AC: 43426 AN: 152156 Hom.: 7013 Cov.: 33 AF XY: 0.284 AC XY: 21118 AN XY: 74380

African (AFR) AF: 0.425 AC: 17631 AN: 41476

American (AMR) AF: 0.362 AC: 5529 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.287 AC: 995 AN: 3466

East Asian (EAS) AF: 0.0201 AC: 104 AN: 5176

South Asian (SAS) AF: 0.246 AC: 1189 AN: 4824

European-Finnish (FIN) AF: 0.201 AC: 2126 AN: 10600

Middle Eastern (MID) AF: 0.255 AC: 75 AN: 294

European-Non Finnish (NFE) AF: 0.222 AC: 15084 AN: 68012

Other (OTH) AF: 0.267 AC: 564 AN: 2110

Alfa AF: 0.254 Hom.: 9674

Bravo AF: 0.302

Asia WGS AF: 0.154 AC: 538 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.0
DANN	Benign	0.75
PhyloP100		0.58
Mutation Taster		=100/0	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs4475146;

hg19: chr4-9946656;