rs4128535

chr6-3328249-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015482.2(SLC22A23):c.914-4247A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.253 in 151,550 control chromosomes in the GnomAD database, including 6,078 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 0.25 (6078 hom., cov: 31)
• Consequence: SLC22A23 NM_015482.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.133

Genes affected

SLC22A23 (HGNC:21106): (solute carrier family 22 member 23) SLC22A23 belongs to a large family of transmembrane proteins that function as uniporters, symporters, and antiporters to transport organic ions across cell membranes (Jacobsson et al., 2007 [PubMed 17714910]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.442 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC22A23	NM_015482.2	c.914-4247A>G		intron_variant		ENST00000406686.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC22A23	ENST00000406686.8	c.914-4247A>G		intron_variant		5	NM_015482.2	P2

Frequencies

GnomAD3 genomes AF: 0.252 AC: 38232 AN: 151432 Hom.: 6054 Cov.: 31

Gnomad AFR AF: 0.446

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.226

Gnomad EAS AF: 0.233

Gnomad SAS AF: 0.272

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.258

Gnomad NFE AF: 0.178

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.253 AC: 38304 AN: 151550 Hom.: 6078 Cov.: 31 AF XY: 0.249 AC XY: 18414 AN XY: 74032

Gnomad4 AFR AF: 0.447

Gnomad4 AMR AF: 0.174

Gnomad4 ASJ AF: 0.226

Gnomad4 EAS AF: 0.233

Gnomad4 SAS AF: 0.272

Gnomad4 FIN AF: 0.0978

Gnomad4 NFE AF: 0.178

Gnomad4 OTH AF: 0.247

Alfa AF: 0.213 Hom.: 522

Bravo AF: 0.267

Asia WGS AF: 0.239 AC: 831 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
Cadd	Benign	4.4
Dann	Benign	0.35

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

Publications

LitVar

Other links and lift over

dbSNP: rs4128535; hg19: chr6-3328483;