NM_004254.4:c.-16G>C

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004254.4(SLC22A8):​c.-16G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000029 in 1,378,688 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000029 (0 hom.)
• Consequence: SLC22A8 NM_004254.4 5_prime_UTR
• Scores: Splicing: ADA: 0.0005497
• 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

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.-16G>C		5_prime_UTR	Exon 2 of 11	NP_004245.2
	SLC22A8	NM_001184732.2		c.-4-12G>C		intron	N/A	NP_001171661.1	Q8TCC7-1
	SLC22A8	NM_001184733.2		c.-25-264G>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.-16G>C		5_prime_UTR	Exon 2 of 11	ENSP00000337335.2	Q8TCC7-1
	SLC22A8	ENST00000430500.6	TSL:1	c.-4-12G>C		intron	N/A	ENSP00000398548.2	Q8TCC7-1
	SLC22A8	ENST00000535878.5	TSL:1	c.-37+755G>C		intron	N/A	ENSP00000443368.1	Q8TCC7-5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00 AC: 0 AN: 191522 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000290 AC: 4 AN: 1378688 Hom.: 0 Cov.: 30 AF XY: 0.00000444 AC XY: 3 AN XY: 675484

African (AFR) AF: 0.00 AC: 0 AN: 31076

American (AMR) AF: 0.00 AC: 0 AN: 34652

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20830

East Asian (EAS) AF: 0.00 AC: 0 AN: 38744

South Asian (SAS) AF: 0.00 AC: 0 AN: 74908

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50078

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5342

European-Non Finnish (NFE) AF: 0.00000375 AC: 4 AN: 1066462

Other (OTH) AF: 0.00 AC: 0 AN: 56596

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.80
PhyloP100		-4.2
PromoterAI		-0.017	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00055
dbscSNV1_RF	Benign	0.018
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -12

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4149179; hg19: chr11-62782446;