11-63014974-C-T

Variant names:

• chr11-63014974-C-T
• rs4149179
• NM_004254.4:c.-16G>A

Variant summary

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

The NM_004254.4(SLC22A8):​c.-16G>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0423 in 1,530,816 control chromosomes in the GnomAD database, including 2,777 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 0.053 (420 hom., cov: 33)
  • Exomes 𝑓: 0.041 (2357 hom.)
• Consequence: SLC22A8 NM_004254.4 5_prime_UTR
• Scores: Splicing: ADA: 0.00009464
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.22
• Publications: 12 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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.234 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A8	NM_004254.4	c.-16G>A		5_prime_UTR_variant	Exon 2 of 11	ENST00000336232.7	NP_004245.2
SLC22A8	NM_001184732.2	c.-4-12G>A		intron_variant	Intron 1 of 10		NP_001171661.1
SLC22A8	NM_001184733.2	c.-25-264G>A		intron_variant	Intron 1 of 10		NP_001171662.1
SLC22A8	NM_001184736.2	c.-37+755G>A		intron_variant	Intron 1 of 9		NP_001171665.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A8	ENST00000336232.7	c.-16G>A		5_prime_UTR_variant	Exon 2 of 11	1	NM_004254.4	ENSP00000337335.2

Frequencies

GnomAD3 genomes AF: 0.0533 AC: 8104 AN: 152096 Hom.: 422 Cov.: 33

Gnomad AFR AF: 0.0561

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.0176

Gnomad EAS AF: 0.246

Gnomad SAS AF: 0.0527

Gnomad FIN AF: 0.0388

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0306

Gnomad OTH AF: 0.0511

GnomAD2 exomes AF: 0.0765 AC: 14660 AN: 191522 AF XY: 0.0703

Gnomad AFR exome AF: 0.0569

Gnomad AMR exome AF: 0.177

Gnomad ASJ exome AF: 0.0240

Gnomad EAS exome AF: 0.259

Gnomad FIN exome AF: 0.0455

Gnomad NFE exome AF: 0.0317

Gnomad OTH exome AF: 0.0525

GnomAD4 exome AF: 0.0411 AC: 56626 AN: 1378602 Hom.: 2357 Cov.: 30 AF XY: 0.0407 AC XY: 27461 AN XY: 675438

African (AFR) AF: 0.0556 AC: 1728 AN: 31076

American (AMR) AF: 0.161 AC: 5577 AN: 34638

Ashkenazi Jewish (ASJ) AF: 0.0201 AC: 419 AN: 20830

East Asian (EAS) AF: 0.238 AC: 9225 AN: 38742

South Asian (SAS) AF: 0.0499 AC: 3740 AN: 74900

European-Finnish (FIN) AF: 0.0418 AC: 2095 AN: 50074

Middle Eastern (MID) AF: 0.0185 AC: 99 AN: 5340

European-Non Finnish (NFE) AF: 0.0292 AC: 31146 AN: 1066410

Other (OTH) AF: 0.0459 AC: 2597 AN: 56592

GnomAD4 genome AF: 0.0532 AC: 8104 AN: 152214 Hom.: 420 Cov.: 33 AF XY: 0.0547 AC XY: 4067 AN XY: 74408

African (AFR) AF: 0.0560 AC: 2327 AN: 41536

American (AMR) AF: 0.103 AC: 1581 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0176 AC: 61 AN: 3470

East Asian (EAS) AF: 0.246 AC: 1268 AN: 5164

South Asian (SAS) AF: 0.0532 AC: 256 AN: 4814

European-Finnish (FIN) AF: 0.0388 AC: 411 AN: 10596

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0306 AC: 2080 AN: 68010

Other (OTH) AF: 0.0501 AC: 106 AN: 2114

Alfa AF: 0.0380 Hom.: 552

Bravo AF: 0.0602

Asia WGS AF: 0.154 AC: 533 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.6
DANN	Benign	0.82
PhyloP100		-4.2
PromoterAI		-0.010	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000095
dbscSNV1_RF	Benign	0.0040
SpliceAI score (max)		0.070		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: rs4149179; hg19: chr11-62782446; COSMIC: COSV60324126; COSMIC: COSV60324126;