chr4-9954455-C-T

Variant names:

• chr4-9954455-C-T
• rs4481233
• NM_020041.3:c.682-12410G>A

Variant summary

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

The NM_020041.3(SLC2A9):​c.682-12410G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.16 in 152,322 control chromosomes in the GnomAD database, including 2,190 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 0.16 (2190 hom., cov: 34)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.233
• Publications: 31 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC2A9	NM_020041.3	c.682-12410G>A		intron_variant	Intron 5 of 11	ENST00000264784.8	NP_064425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8	c.682-12410G>A		intron_variant	Intron 5 of 11	1	NM_020041.3	ENSP00000264784.3
SLC2A9	ENST00000309065.7	c.595-12410G>A		intron_variant	Intron 6 of 12	1		ENSP00000311383.3
SLC2A9	ENST00000505104.5	n.716-12410G>A		intron_variant	Intron 6 of 11	1
SLC2A9	ENST00000506583.5	c.595-12410G>A		intron_variant	Intron 7 of 13	5		ENSP00000422209.1

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24391 AN: 152204 Hom.: 2187 Cov.: 34

Gnomad AFR AF: 0.0943

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.0156

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.173

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.190

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.160 AC: 24402 AN: 152322 Hom.: 2190 Cov.: 34 AF XY: 0.160 AC XY: 11951 AN XY: 74474

African (AFR) AF: 0.0941 AC: 3912 AN: 41586

American (AMR) AF: 0.226 AC: 3464 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.251 AC: 872 AN: 3472

East Asian (EAS) AF: 0.0158 AC: 82 AN: 5184

South Asian (SAS) AF: 0.169 AC: 816 AN: 4834

European-Finnish (FIN) AF: 0.173 AC: 1834 AN: 10612

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.190 AC: 12900 AN: 68014

Other (OTH) AF: 0.164 AC: 347 AN: 2114

Alfa AF: 0.177 Hom.: 7309

Bravo AF: 0.160

Asia WGS AF: 0.0950 AC: 331 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.4
DANN	Benign	0.51
PhyloP100		-0.23
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: rs4481233; hg19: chr4-9956079;