chr6-160216943-T-G

Variant names:

• chr6-160216943-T-G
• rs2450975
• NM_003058.4:c.*489A>C

Variant summary

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

The NM_003058.4(SLC22A2):​c.*489A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.717 in 151,916 control chromosomes in the GnomAD database, including 40,652 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 0.72 (40652 hom., cov: 32)
  • Exomes 𝑓: 0.80 (24 hom.)
  • Failed GnomAD Quality Control
• Consequence: SLC22A2 NM_003058.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.780
• Publications: 11 publications found

Genes affected

SLC22A2 (HGNC:10966): (solute carrier family 22 member 2) 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. This gene is one of three similar cation transporter genes located in a cluster on chromosome 6. The encoded protein contains twelve putative transmembrane domains and is a plasma integral membrane protein. It is found primarily in the kidney, where it may mediate the first step in cation reabsorption. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003058.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A2	NM_003058.4	MANE Select	c.*489A>C		3_prime_UTR	Exon 11 of 11	NP_003049.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A2	ENST00000366953.8	TSL:1 MANE Select	c.*489A>C		3_prime_UTR	Exon 11 of 11	ENSP00000355920.3
	SLC22A2	ENST00000486916.5	TSL:3	n.640+7762A>C		intron	N/A
	SLC22A2	ENST00000498556.1	TSL:5	n.*71A>C		downstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.717 AC: 108914 AN: 151798 Hom.: 40622 Cov.: 32

Gnomad AFR AF: 0.508

Gnomad AMI AF: 0.820

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.840

Gnomad EAS AF: 0.829

Gnomad SAS AF: 0.781

Gnomad FIN AF: 0.836

Gnomad MID AF: 0.755

Gnomad NFE AF: 0.781

Gnomad OTH AF: 0.742

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.803 AC: 61 AN: 76 Hom.: 24 Cov.: 0 AF XY: 0.900 AC XY: 36 AN XY: 40

African (AFR) AF: 1.00 AC: 4 AN: 4

American (AMR) AF: 0.500 AC: 1 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 1.00 AC: 2 AN: 2

European-Finnish (FIN) AF: 1.00 AC: 2 AN: 2

Middle Eastern (MID) AF: 1.00 AC: 2 AN: 2

European-Non Finnish (NFE) AF: 0.767 AC: 46 AN: 60

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.717 AC: 108991 AN: 151916 Hom.: 40652 Cov.: 32 AF XY: 0.725 AC XY: 53846 AN XY: 74224

African (AFR) AF: 0.508 AC: 21007 AN: 41348

American (AMR) AF: 0.824 AC: 12580 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.840 AC: 2915 AN: 3472

East Asian (EAS) AF: 0.829 AC: 4290 AN: 5174

South Asian (SAS) AF: 0.782 AC: 3763 AN: 4814

European-Finnish (FIN) AF: 0.836 AC: 8832 AN: 10564

Middle Eastern (MID) AF: 0.760 AC: 222 AN: 292

European-Non Finnish (NFE) AF: 0.781 AC: 53065 AN: 67972

Other (OTH) AF: 0.746 AC: 1569 AN: 2104

Alfa AF: 0.773 Hom.: 125871

Bravo AF: 0.713

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.2
DANN	Benign	0.68
PhyloP100		-0.78
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: rs2450975; hg19: chr6-160637975;