NM_003057.3:c.411+556G>A

Variant names:

• chr6-160122902-G-A
• rs62440864
• NM_003057.3:c.411+556G>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.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
• 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=-0.95).
• 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 rank	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.411+556G>A		intron_variant	Intron 1 of 10	ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.411+556G>A		intron_variant	Intron 1 of 9		NP_694857.1
SLC22A1	NM_001437335.1	c.411+556G>A		intron_variant	Intron 1 of 8		NP_001424264.1
SLC22A1	XM_005267103.3	c.411+556G>A		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.411+556G>A		intron_variant	Intron 1 of 10	1	NM_003057.3	ENSP00000355930.4

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

African (AFR) AF: 0.0729 AC: 3028 AN: 41536

American (AMR) AF: 0.108 AC: 1646 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3470

East Asian (EAS) AF: 0.00347 AC: 18 AN: 5180

South Asian (SAS) AF: 0.101 AC: 487 AN: 4824

European-Finnish (FIN) AF: 0.172 AC: 1813 AN: 10554

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.171 AC: 11598 AN: 67998

Other (OTH) AF: 0.130 AC: 275 AN: 2114

Alfa AF: 0.143 Hom.: 247

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
PhyloP100		-1.3
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: rs62440864; hg19: chr6-160543934;