6-160154953-C-T

Position:

• chr6-160154953-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003057.3(SLC22A1):​c.1498+43C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 1,419,170 control chromosomes in the GnomAD database, including 106,914 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 0.41 (13456 hom., cov: 31)
  • Exomes 𝑓: 0.38 (93458 hom.)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.64

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

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.516 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.1498+43C>T		intron_variant		ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.1386-1022C>T		intron_variant			NP_694857.1
SLC22A1	XM_005267103.3	c.1498+43C>T		intron_variant			XP_005267160.1
SLC22A1	XM_006715552.3	c.1386-3563C>T		intron_variant			XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.1498+43C>T		intron_variant		1	NM_003057.3	ENSP00000355930	P1

Frequencies

GnomAD3 genomes AF: 0.413 AC: 62700 AN: 151676 Hom.: 13448 Cov.: 31

Gnomad AFR AF: 0.522

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.518

Gnomad EAS AF: 0.329

Gnomad SAS AF: 0.376

Gnomad FIN AF: 0.336

Gnomad MID AF: 0.522

Gnomad NFE AF: 0.384

Gnomad OTH AF: 0.428

GnomAD3 exomes AF: 0.371 AC: 86781 AN: 234008 Hom.: 16549 AF XY: 0.375 AC XY: 47106 AN XY: 125760

Gnomad AFR exome AF: 0.527

Gnomad AMR exome AF: 0.242

Gnomad ASJ exome AF: 0.504

Gnomad EAS exome AF: 0.327

Gnomad SAS exome AF: 0.368

Gnomad FIN exome AF: 0.344

Gnomad NFE exome AF: 0.388

Gnomad OTH exome AF: 0.391

GnomAD4 exome AF: 0.383 AC: 485363 AN: 1267378 Hom.: 93458 Cov.: 17 AF XY: 0.383 AC XY: 244798 AN XY: 638454

Gnomad4 AFR exome AF: 0.532

Gnomad4 AMR exome AF: 0.246

Gnomad4 ASJ exome AF: 0.508

Gnomad4 EAS exome AF: 0.325

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.338

Gnomad4 NFE exome AF: 0.386

Gnomad4 OTH exome AF: 0.399

GnomAD4 genome AF: 0.413 AC: 62745 AN: 151792 Hom.: 13456 Cov.: 31 AF XY: 0.408 AC XY: 30257 AN XY: 74198

Gnomad4 AFR AF: 0.522

Gnomad4 AMR AF: 0.302

Gnomad4 ASJ AF: 0.518

Gnomad4 EAS AF: 0.329

Gnomad4 SAS AF: 0.377

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.384

Gnomad4 OTH AF: 0.425

Alfa AF: 0.394 Hom.: 16806

Bravo AF: 0.417

Asia WGS AF: 0.358 AC: 1243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.066
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs2297374; hg19: chr6-160575985; COSMIC: COSV61451517; COSMIC: COSV61451517;