chr6-160131004-C-G

Variant names:

• chr6-160131004-C-G
• rs4646274
• NM_003057.3:c.515+797C>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.515+797C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0669 in 151,932 control chromosomes in the GnomAD database, including 765 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 0.067 (765 hom., cov: 31)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.170
• Publications: 3 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.364 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	NM_003057.3	MANE Select	c.515+797C>G		intron	N/A	NP_003048.1
	SLC22A1	NM_153187.2		c.515+797C>G		intron	N/A	NP_694857.1
	SLC22A1	NM_001437335.1		c.515+797C>G		intron	N/A	NP_001424264.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC22A1	ENST00000366963.9	TSL:1 MANE Select	c.515+797C>G		intron	N/A	ENSP00000355930.4
	SLC22A1	ENST00000324965.8	TSL:5	c.515+797C>G		intron	N/A	ENSP00000318103.4
	SLC22A1	ENST00000457470.6	TSL:5	c.515+797C>G		intron	N/A	ENSP00000409557.2

Frequencies

GnomAD3 genomes AF: 0.0668 AC: 10148 AN: 151814 Hom.: 764 Cov.: 31

Gnomad AFR AF: 0.0562

Gnomad AMI AF: 0.0110

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.00548

Gnomad EAS AF: 0.379

Gnomad SAS AF: 0.0859

Gnomad FIN AF: 0.0426

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0384

Gnomad OTH AF: 0.0605

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

GnomAD4 genome AF: 0.0669 AC: 10157 AN: 151932 Hom.: 765 Cov.: 31 AF XY: 0.0687 AC XY: 5098 AN XY: 74258

African (AFR) AF: 0.0562 AC: 2326 AN: 41420

American (AMR) AF: 0.148 AC: 2257 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.00548 AC: 19 AN: 3468

East Asian (EAS) AF: 0.378 AC: 1930 AN: 5112

South Asian (SAS) AF: 0.0862 AC: 415 AN: 4814

European-Finnish (FIN) AF: 0.0426 AC: 451 AN: 10580

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0384 AC: 2608 AN: 67966

Other (OTH) AF: 0.0651 AC: 137 AN: 2106

Alfa AF: 0.0217 Hom.: 10

Bravo AF: 0.0788

Asia WGS AF: 0.230 AC: 801 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.6
DANN	Benign	0.67
PhyloP100		0.17
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: rs4646274; hg19: chr6-160552036;