rs874432

Variant names:

• chr4-9918982-T-A
• rs874432
• NM_020041.3:c.1002+1403A>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.1002+1403A>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 151,984 control chromosomes in the GnomAD database, including 7,045 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 0.28 (7045 hom., cov: 32)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.119
• Publications: 7 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: AD, AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• 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 = 0.423 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A9	NM_020041.3	c.1002+1403A>T		intron_variant	Intron 7 of 11	ENST00000264784.8	NP_064425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8	c.1002+1403A>T		intron_variant	Intron 7 of 11	1	NM_020041.3	ENSP00000264784.3
SLC2A9	ENST00000309065.7	c.915+1403A>T		intron_variant	Intron 8 of 12	1		ENSP00000311383.3
SLC2A9	ENST00000505104.5	n.1036+1403A>T		intron_variant	Intron 8 of 11	1
SLC2A9	ENST00000506583.5	c.915+1403A>T		intron_variant	Intron 9 of 13	5		ENSP00000422209.1

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43205 AN: 151866 Hom.: 7034 Cov.: 32

Gnomad AFR AF: 0.428

Gnomad AMI AF: 0.167

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.252

Gnomad EAS AF: 0.0189

Gnomad SAS AF: 0.231

Gnomad FIN AF: 0.183

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.274

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

GnomAD4 genome AF: 0.285 AC: 43253 AN: 151984 Hom.: 7045 Cov.: 32 AF XY: 0.282 AC XY: 20910 AN XY: 74278

African (AFR) AF: 0.428 AC: 17719 AN: 41400

American (AMR) AF: 0.362 AC: 5526 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 874 AN: 3470

East Asian (EAS) AF: 0.0191 AC: 99 AN: 5176

South Asian (SAS) AF: 0.232 AC: 1115 AN: 4810

European-Finnish (FIN) AF: 0.183 AC: 1933 AN: 10582

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15186 AN: 67968

Other (OTH) AF: 0.271 AC: 571 AN: 2108

Alfa AF: 0.256 Hom.: 692

Bravo AF: 0.302

Asia WGS AF: 0.153 AC: 531 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.60
PhyloP100		0.12
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

Other links and lift over

dbSNP: rs874432; hg19: chr4-9920606;