rs62440864

Positions:

• chr6-160122902-G-A

Variant summary

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

The NM_003057.3(SLC22A1):​c.411+556G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.128 in 152,168 control chromosomes in the GnomAD database, including 1,410 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 0.13 (1410 hom., cov: 32)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.26

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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.411+556G>A		intron_variant		ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.411+556G>A		intron_variant			NP_694857.1
SLC22A1	XM_005267103.3	c.411+556G>A		intron_variant			XP_005267160.1
SLC22A1	XM_006715552.3	c.411+556G>A		intron_variant			XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.411+556G>A		intron_variant		1	NM_003057.3	ENSP00000355930	P1

Frequencies

GnomAD3 genomes AF: 0.128 AC: 19464 AN: 152050 Hom.: 1413 Cov.: 32

Gnomad AFR AF: 0.0732

Gnomad AMI AF: 0.0987

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.00347

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.172

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.171

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.128 AC: 19460 AN: 152168 Hom.: 1410 Cov.: 32 AF XY: 0.127 AC XY: 9443 AN XY: 74368

Gnomad4 AFR AF: 0.0729

Gnomad4 AMR AF: 0.108

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.00347

Gnomad4 SAS AF: 0.101

Gnomad4 FIN AF: 0.172

Gnomad4 NFE AF: 0.171

Gnomad4 OTH AF: 0.130

Alfa AF: 0.146 Hom.: 244

Bravo AF: 0.121

Asia WGS AF: 0.0640 AC: 224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.71
DANN	Benign	0.41

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: rs62440864; hg19: chr6-160543934;