2-218381984-C-T

Variant names:

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

Variant summary

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

The ENST00000539932.5(SLC11A1):​n.-385C>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 ENST00000539932.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000468221.5	n.-45C>T		upstream_gene_variant		1
SLC11A1	ENST00000539932.5	n.-385C>T		upstream_gene_variant		1		ENSP00000443435.2
SLC11A1	ENST00000465984.5	n.-204C>T		upstream_gene_variant		2
SLC11A1	ENST00000473367.5	n.-385C>T		upstream_gene_variant		4		ENSP00000484905.1

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

Gnomad4 AFR exome AF: 0.0669

Gnomad4 AMR exome AF: 0.0282

Gnomad4 ASJ exome AF: 0.0478

Gnomad4 EAS exome AF: 0.0404

Gnomad4 SAS exome AF: 0.0452

Gnomad4 FIN exome AF: 0.0435

Gnomad4 NFE exome AF: 0.0499

Gnomad4 OTH exome AF: 0.0460

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

Gnomad4 AFR AF: 0.0800

Gnomad4 AMR AF: 0.0480

Gnomad4 ASJ AF: 0.0569

Gnomad4 EAS AF: 0.0421

Gnomad4 SAS AF: 0.0557

Gnomad4 FIN AF: 0.0468

Gnomad4 NFE AF: 0.0599

Gnomad4 OTH AF: 0.0553

Alfa AF: 0.0532 Hom.: 245

Bravo AF: 0.0622

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	13
DANN	Benign	0.40

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs7573065; hg19: chr2-219246707;