chr4-10018964-C-A

Position:

• chr4-10018964-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_020041.3(SLC2A9):​c.249+11G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00126 in 1,549,042 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00095 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0013 (3 hom.)
• Consequence: SLC2A9 NM_020041.3 intron
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: -0.534

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 4-10018964-C-A is Benign according to our data. Variant chr4-10018964-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 347002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.000952 (145/152322) while in subpopulation AMR AF= 0.00248 (38/15304). AF 95% confidence interval is 0.00186. There are 0 homozygotes in gnomad4. There are 74 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC2A9	NM_020041.3	c.249+11G>T		intron_variant		ENST00000264784.8	NP_064425.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC2A9	ENST00000264784.8	c.249+11G>T		intron_variant		1	NM_020041.3	ENSP00000264784.3

Frequencies

GnomAD3 genomes AF: 0.000953 AC: 145 AN: 152204 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00249

Gnomad ASJ AF: 0.00173

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00122

Gnomad OTH AF: 0.00143

GnomAD3 exomes AF: 0.000929 AC: 141 AN: 151702 Hom.: 0 AF XY: 0.000931 AC XY: 75 AN XY: 80536

Gnomad AFR exome AF: 0.000375

Gnomad AMR exome AF: 0.00105

Gnomad ASJ exome AF: 0.00167

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000791

Gnomad FIN exome AF: 0.0000652

Gnomad NFE exome AF: 0.00121

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00130 AC: 1814 AN: 1396720 Hom.: 3 Cov.: 34 AF XY: 0.00129 AC XY: 887 AN XY: 688892

Gnomad4 AFR exome AF: 0.000190

Gnomad4 AMR exome AF: 0.00120

Gnomad4 ASJ exome AF: 0.00131

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000973

Gnomad4 FIN exome AF: 0.0000205

Gnomad4 NFE exome AF: 0.00145

Gnomad4 OTH exome AF: 0.00133

GnomAD4 genome AF: 0.000952 AC: 145 AN: 152322 Hom.: 0 Cov.: 34 AF XY: 0.000993 AC XY: 74 AN XY: 74486

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.00248

Gnomad4 ASJ AF: 0.00173

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000621

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00122

Gnomad4 OTH AF: 0.00142

Alfa AF: 0.00167 Hom.: 0

Bravo AF: 0.00104

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 24, 2024	- -

Hypouricemia, renal, 2 Benign:2

Likely benign, criteria provided, single submitter	clinical testing	Fulgent Genetics, Fulgent Genetics	Aug 12, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 12, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	8.8
DANN	Benign	0.71
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs377565288; hg19: chr4-10020588;