6-160130061-T-G

Variant names:

• chr6-160130061-T-G
• rs4646272
• NM_003057.3:c.412-43T>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_003057.3(SLC22A1):​c.412-43T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0929 in 1,522,626 control chromosomes in the GnomAD database, including 13,784 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 0.10 (1465 hom., cov: 31)
  • Exomes 𝑓: 0.092 (12319 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• Publications: 33 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.498 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.412-43T>G		intron_variant	Intron 1 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.412-43T>G		intron_variant	Intron 1 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.412-43T>G		intron_variant	Intron 1 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.412-43T>G		intron_variant	Intron 1 of 11		XP_005267160.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.412-43T>G		intron_variant	Intron 1 of 10	1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15399 AN: 152012 Hom.: 1464 Cov.: 31

Gnomad AFR AF: 0.0871

Gnomad AMI AF: 0.0263

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.515

Gnomad SAS AF: 0.178

Gnomad FIN AF: 0.0551

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0671

Gnomad OTH AF: 0.0934

GnomAD2 exomes AF: 0.147 AC: 36714 AN: 250566 AF XY: 0.139

Gnomad AFR exome AF: 0.0871

Gnomad AMR exome AF: 0.316

Gnomad ASJ exome AF: 0.0173

Gnomad EAS exome AF: 0.525

Gnomad FIN exome AF: 0.0597

Gnomad NFE exome AF: 0.0646

Gnomad OTH exome AF: 0.103

GnomAD4 exome AF: 0.0919 AC: 125970 AN: 1370496 Hom.: 12319 Cov.: 21 AF XY: 0.0928 AC XY: 63815 AN XY: 687610

African (AFR) AF: 0.0868 AC: 2747 AN: 31640

American (AMR) AF: 0.300 AC: 13354 AN: 44548

Ashkenazi Jewish (ASJ) AF: 0.0164 AC: 418 AN: 25556

East Asian (EAS) AF: 0.545 AC: 21377 AN: 39232

South Asian (SAS) AF: 0.172 AC: 14547 AN: 84356

European-Finnish (FIN) AF: 0.0596 AC: 3177 AN: 53308

Middle Eastern (MID) AF: 0.0471 AC: 250 AN: 5308

European-Non Finnish (NFE) AF: 0.0630 AC: 64820 AN: 1029282

Other (OTH) AF: 0.0922 AC: 5280 AN: 57266

GnomAD4 genome AF: 0.101 AC: 15415 AN: 152130 Hom.: 1465 Cov.: 31 AF XY: 0.105 AC XY: 7843 AN XY: 74392

African (AFR) AF: 0.0870 AC: 3611 AN: 41482

American (AMR) AF: 0.187 AC: 2856 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0141 AC: 49 AN: 3470

East Asian (EAS) AF: 0.514 AC: 2652 AN: 5158

South Asian (SAS) AF: 0.179 AC: 860 AN: 4814

European-Finnish (FIN) AF: 0.0551 AC: 585 AN: 10608

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0670 AC: 4559 AN: 68006

Other (OTH) AF: 0.0976 AC: 206 AN: 2110

Alfa AF: 0.0803 Hom.: 1732

Bravo AF: 0.113

Asia WGS AF: 0.325 AC: 1130 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.031
DANN	Benign	0.75
PhyloP100		-0.30
PromoterAI		0.0037	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.27		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.27		Position offset: 43

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4646272; hg19: chr6-160551093; COSMIC: COSV61452924;