6-160131222-T-G

Position:

• chr6-160131222-T-G

Variant summary

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

The NM_003057.3(SLC22A1):​c.516-1010T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.665 in 143,524 control chromosomes in the GnomAD database, including 30,420 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 0.66 (30420 hom., cov: 25)
• Consequence: SLC22A1 NM_003057.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.20

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 (EAS) allele frequency at 95% confidence interval = 0.737 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC22A1	NM_003057.3	c.516-1010T>G		intron_variant		ENST00000366963.9	NP_003048.1
SLC22A1	NM_153187.2	c.516-1010T>G		intron_variant			NP_694857.1
SLC22A1	XM_005267103.3	c.516-1010T>G		intron_variant			XP_005267160.1
SLC22A1	XM_006715552.3	c.516-1010T>G		intron_variant			XP_006715615.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC22A1	ENST00000366963.9	c.516-1010T>G		intron_variant		1	NM_003057.3	ENSP00000355930.4

Frequencies

GnomAD3 genomes AF: 0.665 AC: 95321 AN: 143420 Hom.: 30392 Cov.: 25

Gnomad AFR AF: 0.700

Gnomad AMI AF: 0.646

Gnomad AMR AF: 0.748

Gnomad ASJ AF: 0.684

Gnomad EAS AF: 0.750

Gnomad SAS AF: 0.656

Gnomad FIN AF: 0.611

Gnomad MID AF: 0.750

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.686

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

GnomAD4 genome AF: 0.665 AC: 95404 AN: 143524 Hom.: 30420 Cov.: 25 AF XY: 0.667 AC XY: 46616 AN XY: 69882

Gnomad4 AFR AF: 0.700

Gnomad4 AMR AF: 0.748

Gnomad4 ASJ AF: 0.684

Gnomad4 EAS AF: 0.750

Gnomad4 SAS AF: 0.656

Gnomad4 FIN AF: 0.611

Gnomad4 NFE AF: 0.625

Gnomad4 OTH AF: 0.688

Alfa AF: 0.553 Hom.: 2931

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.50
DANN	Benign	0.50

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: rs614890; hg19: chr6-160552254; COSMIC: COSV61453482;