chr5-132320824-A-G

Variant names:

• chr5-132320824-A-G
• rs272842
• NM_003059.3:c.653-1360A>G

Variant summary

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

The NM_003059.3(SLC22A4):​c.653-1360A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.597 in 152,084 control chromosomes in the GnomAD database, including 27,737 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 0.60 (27736 hom., cov: 33)
  • Exomes 𝑓: 0.50 (1 hom.)
• Consequence: SLC22A4 NM_003059.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.286
• Publications: 23 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A4	NM_003059.3	c.653-1360A>G		intron_variant	Intron 3 of 9	ENST00000200652.4	NP_003050.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A4	ENST00000200652.4	c.653-1360A>G		intron_variant	Intron 3 of 9	1	NM_003059.3	ENSP00000200652.3
MIR3936HG	ENST00000621103.4	n.825-8571T>C		intron_variant	Intron 7 of 7	1
SLC22A4	ENST00000491257.1	n.457-41A>G		intron_variant	Intron 3 of 3	4
MIR3936HG	ENST00000669845.1	n.451-8571T>C		intron_variant	Intron 3 of 3

Frequencies

GnomAD3 genomes AF: 0.597 AC: 90784 AN: 151958 Hom.: 27707 Cov.: 33

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.760

Gnomad AMR AF: 0.650

Gnomad ASJ AF: 0.585

Gnomad EAS AF: 0.331

Gnomad SAS AF: 0.360

Gnomad FIN AF: 0.487

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.604

Gnomad OTH AF: 0.610

GnomAD4 exome AF: 0.500 AC: 4 AN: 8 Hom.: 1 Cov.: 0 AF XY: 0.500 AC XY: 4 AN XY: 8

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.500 AC: 4 AN: 8

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.598 AC: 90866 AN: 152076 Hom.: 27736 Cov.: 33 AF XY: 0.586 AC XY: 43598 AN XY: 74340

African (AFR) AF: 0.655 AC: 27154 AN: 41462

American (AMR) AF: 0.649 AC: 9919 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.585 AC: 2030 AN: 3472

East Asian (EAS) AF: 0.331 AC: 1706 AN: 5156

South Asian (SAS) AF: 0.358 AC: 1729 AN: 4826

European-Finnish (FIN) AF: 0.487 AC: 5160 AN: 10586

Middle Eastern (MID) AF: 0.527 AC: 155 AN: 294

European-Non Finnish (NFE) AF: 0.604 AC: 41035 AN: 67984

Other (OTH) AF: 0.610 AC: 1286 AN: 2108

Alfa AF: 0.611 Hom.: 48347

Bravo AF: 0.619

Asia WGS AF: 0.383 AC: 1335 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	9.7
DANN	Benign	0.84
PhyloP100		0.29
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: rs272842; hg19: chr5-131656517;