rs7929627

chr11-64600264-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_144585.4(SLC22A12):c.1286-103A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 927,968 control chromosomes in the GnomAD database, including 32,145 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.33 (10869 hom., cov: 33)
  • Exomes 𝑓: 0.22 (21276 hom.)
• Consequence: SLC22A12 NM_144585.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.435

Genes affected

SLC22A12 (HGNC:17989): (solute carrier family 22 member 12) The protein encoded by this gene is a member of the organic anion transporter (OAT) family, and it acts as a urate transporter to regulate urate levels in blood. This protein is an integral membrane protein primarily found in epithelial cells of the proximal tubule of the kidney. An elevated level of serum urate, hyperuricemia, is associated with increased incidences of gout, and mutations in this gene cause renal hypouricemia type 1. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2013]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-64600264-A-G is Benign according to our data. Variant chr11-64600264-A-G is described in ClinVar as [Benign]. Clinvar id is 1262572.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.6 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A12	NM_144585.4	c.1286-103A>G		intron_variant		ENST00000377574.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A12	ENST00000377574.6	c.1286-103A>G		intron_variant		1	NM_144585.4	P1

Frequencies

GnomAD3 genomes AF: 0.331 AC: 50381 AN: 151988 Hom.: 10836 Cov.: 33

Gnomad AFR AF: 0.606

Gnomad AMI AF: 0.127

Gnomad AMR AF: 0.241

Gnomad ASJ AF: 0.167

Gnomad EAS AF: 0.477

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.215

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.215 AC: 166845 AN: 775862 Hom.: 21276 AF XY: 0.213 AC XY: 86163 AN XY: 405088

Gnomad4 AFR exome AF: 0.597

Gnomad4 AMR exome AF: 0.236

Gnomad4 ASJ exome AF: 0.174

Gnomad4 EAS exome AF: 0.475

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.279

Gnomad4 NFE exome AF: 0.180

Gnomad4 OTH exome AF: 0.240

GnomAD4 genome AF: 0.332 AC: 50458 AN: 152106 Hom.: 10869 Cov.: 33 AF XY: 0.332 AC XY: 24693 AN XY: 74346

Gnomad4 AFR AF: 0.606

Gnomad4 AMR AF: 0.241

Gnomad4 ASJ AF: 0.167

Gnomad4 EAS AF: 0.477

Gnomad4 SAS AF: 0.219

Gnomad4 FIN AF: 0.297

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.284

Alfa AF: 0.317 Hom.: 1477

Bravo AF: 0.341

Asia WGS AF: 0.351 AC: 1220 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 20, 2019

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	5.8
Dann	Benign	0.53

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: rs7929627; hg19: chr11-64367736; COSMIC: COSV60573756;