2-218381926-CGTGTGTGT-CGTGTGTGTGT

Variant names:

• chr2-218381926-C-CGT
• rs34448891
• ENST00000468221.5:n.-103_-102insGT

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000468221.5(SLC11A1):​n.-103_-102insGT variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 184,466 control chromosomes in the GnomAD database, including 4,890 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.25 (4691 hom., cov: 21)
  • Exomes 𝑓: 0.20 (199 hom.)
• Consequence: SLC11A1 ENST00000468221.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 14 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.298 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.-103_-102insGT		upstream_gene	N/A
	SLC11A1	ENST00000473367.5	TSL:4	n.-443_-442insGT		upstream_gene	N/A	ENSP00000484905.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 37104 AN: 148560 Hom.: 4687 Cov.: 21

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.351

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.282

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.298

Gnomad MID AF: 0.321

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.275

GnomAD4 exome AF: 0.199 AC: 7116 AN: 35818 Hom.: 199 AF XY: 0.195 AC XY: 3725 AN XY: 19074

African (AFR) AF: 0.163 AC: 159 AN: 976

American (AMR) AF: 0.214 AC: 209 AN: 978

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 212 AN: 1086

East Asian (EAS) AF: 0.120 AC: 309 AN: 2578

South Asian (SAS) AF: 0.151 AC: 424 AN: 2814

European-Finnish (FIN) AF: 0.230 AC: 776 AN: 3378

Middle Eastern (MID) AF: 0.254 AC: 36 AN: 142

European-Non Finnish (NFE) AF: 0.210 AC: 4566 AN: 21746

Other (OTH) AF: 0.200 AC: 425 AN: 2120

GnomAD4 genome AF: 0.250 AC: 37122 AN: 148648 Hom.: 4691 Cov.: 21 AF XY: 0.251 AC XY: 18180 AN XY: 72376

African (AFR) AF: 0.196 AC: 7917 AN: 40448

American (AMR) AF: 0.306 AC: 4548 AN: 14872

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 968 AN: 3428

East Asian (EAS) AF: 0.127 AC: 641 AN: 5062

South Asian (SAS) AF: 0.183 AC: 861 AN: 4698

European-Finnish (FIN) AF: 0.298 AC: 2944 AN: 9890

Middle Eastern (MID) AF: 0.311 AC: 89 AN: 286

European-Non Finnish (NFE) AF: 0.273 AC: 18273 AN: 67014

Other (OTH) AF: 0.275 AC: 564 AN: 2048

Alfa AF: 0.0797 Hom.: 139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.18

Splicing

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

Other links and lift over

dbSNP: rs34448891; hg19: chr2-219246649;