6-160131222-T-G

Variant names:

• chr6-160131222-T-G
• rs614890
• NM_003057.3:c.516-1010T>G

Variant summary

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

The NM_003057.3(SLC22A1):​c.516-1010T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 143,524 control chromosomes in the GnomAD database, including 30,420 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 0.66 (30420 hom., cov: 25)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20
• Publications: 4 publications found

Genes affected

SLC22A1 (HGNC:10963): (solute carrier family 22 member 1) 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. Two transcript variants encoding two different isoforms have been found for this gene, but only the longer variant encodes a functional transporter. [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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003057.3. 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
	SLC22A1	NM_003057.3	MANE Select	c.516-1010T>G		intron	N/A	NP_003048.1	O15245-1
	SLC22A1	NM_153187.2		c.516-1010T>G		intron	N/A	NP_694857.1	O15245-2
	SLC22A1	NM_001437335.1		c.516-1010T>G		intron	N/A	NP_001424264.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.516-1010T>G		intron	N/A	ENSP00000355930.4	O15245-1
	SLC22A1	ENST00000898298.1		c.630-1010T>G		intron	N/A	ENSP00000568357.1
	SLC22A1	ENST00000898304.1		c.516-1010T>G		intron	N/A	ENSP00000568363.1

Frequencies

GnomAD3 genomes AF: 0.665 AC: 95321 AN: 143420 Hom.: 30392 Cov.: 25

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.665 AC: 95404 AN: 143524 Hom.: 30420 Cov.: 25 AF XY: 0.667 AC XY: 46616 AN XY: 69882

African (AFR) AF: 0.700 AC: 27029 AN: 38608

American (AMR) AF: 0.748 AC: 11050 AN: 14766

Ashkenazi Jewish (ASJ) AF: 0.684 AC: 2295 AN: 3354

East Asian (EAS) AF: 0.750 AC: 3677 AN: 4904

South Asian (SAS) AF: 0.656 AC: 2932 AN: 4472

European-Finnish (FIN) AF: 0.611 AC: 5836 AN: 9544

Middle Eastern (MID) AF: 0.755 AC: 219 AN: 290

European-Non Finnish (NFE) AF: 0.625 AC: 40429 AN: 64718

Other (OTH) AF: 0.688 AC: 1384 AN: 2012

Alfa AF: 0.594 Hom.: 7270

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50
DANN	Benign	0.50
PhyloP100		-2.2
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: rs614890; hg19: chr6-160552254; COSMIC: COSV61453482;