ENST00000468221.5:n.-45C>T

Variant names:

• chr2-218381984-C-T
• rs7573065
• ENST00000468221.5:n.-45C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000468221.5(SLC11A1):​n.-45C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 282,344 control chromosomes in the GnomAD database, including 496 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 0.063 (312 hom., cov: 31)
  • Exomes 𝑓: 0.048 (184 hom.)
• Consequence: SLC11A1 ENST00000468221.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 28 publications found

Genes affected

SLC11A1 (HGNC:10907): (solute carrier family 11 member 1) This gene is a member of the solute carrier family 11 (proton-coupled divalent metal ion transporters) family and encodes a multi-pass membrane protein. The protein functions as a divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Mutations in this gene have been associated with susceptibility to infectious diseases such as tuberculosis and leprosy, and inflammatory diseases such as rheumatoid arthritis and Crohn disease. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

SLC11A1 Gene-Disease associations (from GenCC):

• cystic fibrosis

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000468221.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	ENST00000468221.5	TSL:1	n.-45C>T		upstream_gene	N/A
	SLC11A1	ENST00000539932.5	TSL:1	n.-385C>T		upstream_gene	N/A	ENSP00000443435.2
	SLC11A1	ENST00000465984.5	TSL:2	n.-204C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0626 AC: 9455 AN: 150988 Hom.: 312 Cov.: 31

Gnomad AFR AF: 0.0801

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.0481

Gnomad ASJ AF: 0.0569

Gnomad EAS AF: 0.0420

Gnomad SAS AF: 0.0563

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.0223

Gnomad NFE AF: 0.0599

Gnomad OTH AF: 0.0559

GnomAD4 exome AF: 0.0478 AC: 6270 AN: 131240 Hom.: 184 Cov.: 0 AF XY: 0.0469 AC XY: 3226 AN XY: 68788

African (AFR) AF: 0.0669 AC: 255 AN: 3812

American (AMR) AF: 0.0282 AC: 119 AN: 4214

Ashkenazi Jewish (ASJ) AF: 0.0478 AC: 203 AN: 4246

East Asian (EAS) AF: 0.0404 AC: 353 AN: 8740

South Asian (SAS) AF: 0.0452 AC: 521 AN: 11518

European-Finnish (FIN) AF: 0.0435 AC: 467 AN: 10744

Middle Eastern (MID) AF: 0.0319 AC: 19 AN: 596

European-Non Finnish (NFE) AF: 0.0499 AC: 3974 AN: 79572

Other (OTH) AF: 0.0460 AC: 359 AN: 7798

GnomAD4 genome AF: 0.0626 AC: 9457 AN: 151104 Hom.: 312 Cov.: 31 AF XY: 0.0614 AC XY: 4523 AN XY: 73692

African (AFR) AF: 0.0800 AC: 3286 AN: 41086

American (AMR) AF: 0.0480 AC: 727 AN: 15144

Ashkenazi Jewish (ASJ) AF: 0.0569 AC: 197 AN: 3462

East Asian (EAS) AF: 0.0421 AC: 217 AN: 5156

South Asian (SAS) AF: 0.0557 AC: 267 AN: 4790

European-Finnish (FIN) AF: 0.0468 AC: 485 AN: 10354

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0599 AC: 4062 AN: 67814

Other (OTH) AF: 0.0553 AC: 116 AN: 2098

Alfa AF: 0.0571 Hom.: 422

Bravo AF: 0.0622

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.40
PhyloP100		0.077
PromoterAI		-0.16	Neutral

Splicing

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

Other links and lift over

dbSNP: rs7573065; hg19: chr2-219246707;