4-9980567-C-T

Variant names:

• chr4-9980567-C-T
• rs13115193
• NM_020041.3:c.681+25G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000264784.8(SLC2A9):​c.681+25G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 1,613,260 control chromosomes in the GnomAD database, including 205,376 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14795 hom., cov: 33)
  • Exomes 𝑓: 0.51 (190581 hom.)
• Consequence: SLC2A9 ENST00000264784.8 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.92
• 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: 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 4-9980567-C-T is Benign according to our data. Variant chr4-9980567-C-T is described in ClinVar as Benign. ClinVar VariationId is 1287173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264784.8. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A9	NM_020041.3	MANE Select	c.681+25G>A		intron	N/A	NP_064425.2
	SLC2A9	NM_001001290.2		c.594+25G>A		intron	N/A	NP_001001290.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC2A9	ENST00000264784.8	TSL:1 MANE Select	c.681+25G>A		intron	N/A	ENSP00000264784.3
	SLC2A9	ENST00000309065.7	TSL:1	c.594+25G>A		intron	N/A	ENSP00000311383.3
	SLC2A9	ENST00000505104.5	TSL:1	n.715+25G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.422 AC: 64153 AN: 151930 Hom.: 14788 Cov.: 33

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.628

Gnomad AMR AF: 0.396

Gnomad ASJ AF: 0.509

Gnomad EAS AF: 0.423

Gnomad SAS AF: 0.506

Gnomad FIN AF: 0.516

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.521

Gnomad OTH AF: 0.441

GnomAD2 exomes AF: 0.472 AC: 118272 AN: 250514 AF XY: 0.482

Gnomad AFR exome AF: 0.215

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.525

Gnomad EAS exome AF: 0.424

Gnomad FIN exome AF: 0.521

Gnomad NFE exome AF: 0.520

Gnomad OTH exome AF: 0.492

GnomAD4 exome AF: 0.507 AC: 741096 AN: 1461212 Hom.: 190581 Cov.: 47 AF XY: 0.509 AC XY: 369771 AN XY: 726934

African (AFR) AF: 0.212 AC: 7100 AN: 33460

American (AMR) AF: 0.377 AC: 16847 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.525 AC: 13725 AN: 26134

East Asian (EAS) AF: 0.431 AC: 17111 AN: 39694

South Asian (SAS) AF: 0.510 AC: 43999 AN: 86206

European-Finnish (FIN) AF: 0.524 AC: 28000 AN: 53392

Middle Eastern (MID) AF: 0.473 AC: 2643 AN: 5588

European-Non Finnish (NFE) AF: 0.524 AC: 582187 AN: 1111666

Other (OTH) AF: 0.488 AC: 29484 AN: 60358

GnomAD4 genome AF: 0.422 AC: 64158 AN: 152048 Hom.: 14795 Cov.: 33 AF XY: 0.423 AC XY: 31420 AN XY: 74324

African (AFR) AF: 0.223 AC: 9263 AN: 41480

American (AMR) AF: 0.396 AC: 6054 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.509 AC: 1765 AN: 3470

East Asian (EAS) AF: 0.423 AC: 2181 AN: 5162

South Asian (SAS) AF: 0.507 AC: 2445 AN: 4824

European-Finnish (FIN) AF: 0.516 AC: 5451 AN: 10564

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.521 AC: 35373 AN: 67950

Other (OTH) AF: 0.440 AC: 930 AN: 2112

Alfa AF: 0.459 Hom.: 3500

Bravo AF: 0.405

Asia WGS AF: 0.465 AC: 1615 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Hypouricemia, renal, 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.0090
DANN	Benign	0.59
PhyloP100		-1.9
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: rs13115193; hg19: chr4-9982191; COSMIC: COSV53328253; COSMIC: COSV53328253;