11-62998397-A-G

Variant names:

• chr11-62998397-A-G
• rs4149183
• NM_004254.4:c.761+524T>C

Variant summary

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

The NM_004254.4(SLC22A8):​c.761+524T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 151,892 control chromosomes in the GnomAD database, including 5,860 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 0.26 (5860 hom., cov: 32)
• Consequence: SLC22A8 NM_004254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.294
• Publications: 6 publications found

Genes affected

SLC22A8 (HGNC:10972): (solute carrier family 22 member 8) This gene encodes a protein involved in the sodium-independent transport and excretion of organic anions, some of which are potentially toxic. The encoded protein is an integral membrane protein and appears to be localized to the basolateral membrane of the kidney. Multiple alternatively spliced transcript variants that encode different protein isoforms have been described for this gene. [provided by RefSeq, May 2010]

ENSG00000301851 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.373 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004254.4. 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
	SLC22A8	NM_004254.4	MANE Select	c.761+524T>C		intron	N/A	NP_004245.2
	SLC22A8	NM_001184732.2		c.761+524T>C		intron	N/A	NP_001171661.1
	SLC22A8	NM_001184733.2		c.488+524T>C		intron	N/A	NP_001171662.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A8	ENST00000336232.7	TSL:1 MANE Select	c.761+524T>C		intron	N/A	ENSP00000337335.2
	SLC22A8	ENST00000430500.6	TSL:1	c.761+524T>C		intron	N/A	ENSP00000398548.2
	SLC22A8	ENST00000311438.12	TSL:1	c.761+524T>C		intron	N/A	ENSP00000311463.8

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39897 AN: 151774 Hom.: 5825 Cov.: 32

Gnomad AFR AF: 0.377

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.328

Gnomad SAS AF: 0.168

Gnomad FIN AF: 0.242

Gnomad MID AF: 0.226

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.263 AC: 39979 AN: 151892 Hom.: 5860 Cov.: 32 AF XY: 0.262 AC XY: 19425 AN XY: 74232

African (AFR) AF: 0.378 AC: 15663 AN: 41408

American (AMR) AF: 0.172 AC: 2622 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3464

East Asian (EAS) AF: 0.329 AC: 1690 AN: 5142

South Asian (SAS) AF: 0.168 AC: 807 AN: 4806

European-Finnish (FIN) AF: 0.242 AC: 2547 AN: 10542

Middle Eastern (MID) AF: 0.229 AC: 67 AN: 292

European-Non Finnish (NFE) AF: 0.222 AC: 15107 AN: 67946

Other (OTH) AF: 0.253 AC: 534 AN: 2112

Alfa AF: 0.233 Hom.: 14244

Bravo AF: 0.265

Asia WGS AF: 0.236 AC: 820 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	7.1
DANN	Benign	0.75
PhyloP100		-0.29
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs4149183; hg19: chr11-62765869;