11-63000641-C-A

Variant names:

• chr11-63000641-C-A
• rs4149182
• NM_004254.4:c.437+79G>T

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.437+79G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000023 in 868,522 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: 31)
  • Exomes 𝑓: 0.0000023 (0 hom.)
• Consequence: SLC22A8 NM_004254.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.10
• Publications: 0 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=-0.89).

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>T		intron	N/A	NP_004245.2
	SLC22A8	NM_001184732.2		c.437+79G>T		intron	N/A	NP_001171661.1	Q8TCC7-1
	SLC22A8	NM_001184733.2		c.164+79G>T		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>T		intron	N/A	ENSP00000337335.2	Q8TCC7-1
	SLC22A8	ENST00000430500.6	TSL:1	c.437+79G>T		intron	N/A	ENSP00000398548.2	Q8TCC7-1
	SLC22A8	ENST00000311438.12	TSL:1	c.437+79G>T		intron	N/A	ENSP00000311463.8	H7BXN9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000230 AC: 2 AN: 868522 Hom.: 0 AF XY: 0.00000222 AC XY: 1 AN XY: 449914

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 21904

American (AMR) AF: 0.00 AC: 0 AN: 39302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 20878

East Asian (EAS) AF: 0.00 AC: 0 AN: 35270

South Asian (SAS) AF: 0.00 AC: 0 AN: 68772

European-Finnish (FIN) AF: 0.0000215 AC: 1 AN: 46496

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4558

European-Non Finnish (NFE) AF: 0.00000169 AC: 1 AN: 590722

Other (OTH) AF: 0.00 AC: 0 AN: 40620

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.33
PhyloP100		-1.1

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;