11-63000641-C-G

Variant names:

• chr11-63000641-C-G
• rs4149182
• NM_004254.4:c.437+79G>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.437+79G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 1,018,738 control chromosomes in the GnomAD database, including 28,287 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 (5870 hom., cov: 31)
  • Exomes 𝑓: 0.22 (22417 hom.)
• Consequence: SLC22A8 NM_004254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 15 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 = 0.375 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A8	NM_004254.4	MANE Select	c.437+79G>C		intron	N/A	NP_004245.2
	SLC22A8	NM_001184732.2		c.437+79G>C		intron	N/A	NP_001171661.1	Q8TCC7-1
	SLC22A8	NM_001184733.2		c.164+79G>C		intron	N/A	NP_001171662.1	Q8TCC7-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A8	ENST00000336232.7	TSL:1 MANE Select	c.437+79G>C		intron	N/A	ENSP00000337335.2	Q8TCC7-1
	SLC22A8	ENST00000430500.6	TSL:1	c.437+79G>C		intron	N/A	ENSP00000398548.2	Q8TCC7-1
	SLC22A8	ENST00000311438.12	TSL:1	c.437+79G>C		intron	N/A	ENSP00000311463.8	H7BXN9

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39949 AN: 151790 Hom.: 5832 Cov.: 31

Gnomad AFR AF: 0.379

Gnomad AMI AF: 0.328

Gnomad AMR AF: 0.171

Gnomad ASJ AF: 0.186

Gnomad EAS AF: 0.327

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.240

Gnomad MID AF: 0.229

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.221 AC: 191636 AN: 866830 Hom.: 22417 AF XY: 0.217 AC XY: 97596 AN XY: 449026

African (AFR) AF: 0.383 AC: 8373 AN: 21860

American (AMR) AF: 0.122 AC: 4799 AN: 39280

Ashkenazi Jewish (ASJ) AF: 0.185 AC: 3860 AN: 20862

East Asian (EAS) AF: 0.335 AC: 11785 AN: 35226

South Asian (SAS) AF: 0.158 AC: 10874 AN: 68698

European-Finnish (FIN) AF: 0.240 AC: 11143 AN: 46396

Middle Eastern (MID) AF: 0.264 AC: 1201 AN: 4550

European-Non Finnish (NFE) AF: 0.221 AC: 130393 AN: 589396

Other (OTH) AF: 0.227 AC: 9208 AN: 40562

GnomAD4 genome AF: 0.264 AC: 40038 AN: 151908 Hom.: 5870 Cov.: 31 AF XY: 0.262 AC XY: 19446 AN XY: 74240

African (AFR) AF: 0.380 AC: 15730 AN: 41378

American (AMR) AF: 0.171 AC: 2616 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.186 AC: 644 AN: 3468

East Asian (EAS) AF: 0.328 AC: 1687 AN: 5148

South Asian (SAS) AF: 0.169 AC: 813 AN: 4814

European-Finnish (FIN) AF: 0.240 AC: 2540 AN: 10568

Middle Eastern (MID) AF: 0.233 AC: 68 AN: 292

European-Non Finnish (NFE) AF: 0.222 AC: 15107 AN: 67938

Other (OTH) AF: 0.253 AC: 535 AN: 2112

Alfa AF: 0.136 Hom.: 272

Bravo AF: 0.265

Asia WGS AF: 0.238 AC: 828 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.46
DANN	Benign	0.52
PhyloP100		-1.1
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: rs4149182; hg19: chr11-62768113; COSMIC: COSV60326237; COSMIC: COSV60326237;