chr6-160136122-G-A

Variant names:

• chr6-160136122-G-A
• rs4646276
• NM_003057.3:c.840-98G>A

Variant summary

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

The NM_003057.3(SLC22A1):​c.840-98G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.118 in 901,180 control chromosomes in the GnomAD database, including 9,573 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 0.12 (1608 hom., cov: 32)
  • Exomes 𝑓: 0.12 (7965 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0960
• Publications: 7 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 = 0.388 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.840-98G>A		intron_variant	Intron 4 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.840-98G>A		intron_variant	Intron 4 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.840-98G>A		intron_variant	Intron 4 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.840-98G>A		intron_variant	Intron 4 of 11		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.840-98G>A		intron_variant	Intron 4 of 10	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18744 AN: 152096 Hom.: 1606 Cov.: 32

Gnomad AFR AF: 0.139

Gnomad AMI AF: 0.0395

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.0878

Gnomad EAS AF: 0.404

Gnomad SAS AF: 0.151

Gnomad FIN AF: 0.0646

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0823

Gnomad OTH AF: 0.131

GnomAD4 exome AF: 0.117 AC: 87356 AN: 748966 Hom.: 7965 AF XY: 0.116 AC XY: 45385 AN XY: 390522

African (AFR) AF: 0.142 AC: 2846 AN: 20040

American (AMR) AF: 0.294 AC: 10031 AN: 34110

Ashkenazi Jewish (ASJ) AF: 0.0876 AC: 1652 AN: 18854

East Asian (EAS) AF: 0.421 AC: 15009 AN: 35658

South Asian (SAS) AF: 0.150 AC: 9567 AN: 63582

European-Finnish (FIN) AF: 0.0700 AC: 3463 AN: 49494

Middle Eastern (MID) AF: 0.107 AC: 384 AN: 3600

European-Non Finnish (NFE) AF: 0.0822 AC: 40067 AN: 487146

Other (OTH) AF: 0.119 AC: 4337 AN: 36482

GnomAD4 genome AF: 0.123 AC: 18766 AN: 152214 Hom.: 1608 Cov.: 32 AF XY: 0.124 AC XY: 9261 AN XY: 74430

African (AFR) AF: 0.139 AC: 5763 AN: 41528

American (AMR) AF: 0.214 AC: 3267 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0878 AC: 305 AN: 3472

East Asian (EAS) AF: 0.402 AC: 2076 AN: 5160

South Asian (SAS) AF: 0.150 AC: 725 AN: 4826

European-Finnish (FIN) AF: 0.0646 AC: 685 AN: 10610

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0823 AC: 5595 AN: 68014

Other (OTH) AF: 0.136 AC: 288 AN: 2112

Alfa AF: 0.0794 Hom.: 219

Bravo AF: 0.140

Asia WGS AF: 0.281 AC: 976 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.8
DANN	Benign	0.47
PhyloP100		0.096
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: rs4646276; hg19: chr6-160557154; COSMIC: COSV61453788; COSMIC: COSV61453788;