5-132324426-G-C

Variant names:

• chr5-132324426-G-C
• rs273915
• NM_003059.3:c.824+2071G>C

Variant summary

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

The NM_003059.3(SLC22A4):​c.824+2071G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.659 in 446,188 control chromosomes in the GnomAD database, including 99,654 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 0.71 (38381 hom., cov: 28)
  • Exomes 𝑓: 0.64 (61273 hom.)
• Consequence: SLC22A4 NM_003059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.265
• Publications: 18 publications found

Genes affected

SLC22A4 (HGNC:10968): (solute carrier family 22 member 4) Polyspecific organic cation transporters in the liver, kidney, intestine, and other organs are critical for elimination of many endogenous small organic cations as well as a wide array of drugs and environmental toxins. The encoded protein is an organic cation transporter and plasma integral membrane protein containing eleven putative transmembrane domains as well as a nucleotide-binding site motif. Transport by this protein is at least partially ATP-dependent. [provided by RefSeq, Jul 2008]

MIR3936HG (HGNC:40538): (MIR3936 host gene)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.824+2071G>C		intron_variant	Intron 4 of 9	ENST00000200652.4	NP_003050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.824+2071G>C		intron_variant	Intron 4 of 9	1	NM_003059.3	ENSP00000200652.3
MIR3936HG	ENST00000621103.4	n.824+7763C>G		intron_variant	Intron 7 of 7	1
SLC22A4	ENST00000425923.1	n.173-35G>C		intron_variant	Intron 1 of 2	3
MIR3936HG	ENST00000669845.1	n.450+7763C>G		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.706 AC: 107076 AN: 151668 Hom.: 38348 Cov.: 28

Gnomad AFR AF: 0.806

Gnomad AMI AF: 0.870

Gnomad AMR AF: 0.709

Gnomad ASJ AF: 0.699

Gnomad EAS AF: 0.622

Gnomad SAS AF: 0.442

Gnomad FIN AF: 0.572

Gnomad MID AF: 0.580

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.709

GnomAD2 exomes AF: 0.650 AC: 86056 AN: 132432 AF XY: 0.633

Gnomad AFR exome AF: 0.809

Gnomad AMR exome AF: 0.724

Gnomad ASJ exome AF: 0.707

Gnomad EAS exome AF: 0.634

Gnomad FIN exome AF: 0.573

Gnomad NFE exome AF: 0.701

Gnomad OTH exome AF: 0.668

GnomAD4 exome AF: 0.635 AC: 187087 AN: 294402 Hom.: 61273 Cov.: 0 AF XY: 0.615 AC XY: 101799 AN XY: 165620

African (AFR) AF: 0.808 AC: 6190 AN: 7660

American (AMR) AF: 0.721 AC: 17115 AN: 23728

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 6796 AN: 9514

East Asian (EAS) AF: 0.641 AC: 5711 AN: 8904

South Asian (SAS) AF: 0.440 AC: 25117 AN: 57082

European-Finnish (FIN) AF: 0.571 AC: 15047 AN: 26370

Middle Eastern (MID) AF: 0.605 AC: 708 AN: 1170

European-Non Finnish (NFE) AF: 0.692 AC: 101694 AN: 146882

Other (OTH) AF: 0.665 AC: 8709 AN: 13092

GnomAD4 genome AF: 0.706 AC: 107164 AN: 151786 Hom.: 38381 Cov.: 28 AF XY: 0.694 AC XY: 51498 AN XY: 74170

African (AFR) AF: 0.806 AC: 33374 AN: 41400

American (AMR) AF: 0.709 AC: 10818 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.699 AC: 2426 AN: 3472

East Asian (EAS) AF: 0.621 AC: 3190 AN: 5134

South Asian (SAS) AF: 0.440 AC: 2108 AN: 4788

European-Finnish (FIN) AF: 0.572 AC: 5990 AN: 10480

Middle Eastern (MID) AF: 0.599 AC: 175 AN: 292

European-Non Finnish (NFE) AF: 0.689 AC: 46794 AN: 67934

Other (OTH) AF: 0.709 AC: 1496 AN: 2110

Alfa AF: 0.639 Hom.: 3759

Bravo AF: 0.728

Asia WGS AF: 0.525 AC: 1828 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	2.3
DANN	Benign	0.66
PhyloP100		-0.27
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: rs273915; hg19: chr5-131660119; COSMIC: COSV52360975; COSMIC: COSV52360975;