rs17235416

Positions:

• chr2-218395090-ATGTG-A

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_000578.4(SLC11A1):​c.*56_*59del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0355 in 1,370,208 control chromosomes in the GnomAD database, including 2,602 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.082 (1034 hom., cov: 32)
  • Exomes 𝑓: 0.030 (1568 hom.)
• Consequence: SLC11A1 NM_000578.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.383

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A1	NM_000578.4	c.*56_*59del		3_prime_UTR_variant	15/15	ENST00000233202.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A1	ENST00000233202.11	c.*56_*59del		3_prime_UTR_variant	15/15	1	NM_000578.4	P1
SLC11A1	ENST00000468221.5	n.4836_4839del		non_coding_transcript_exon_variant	13/13	1
SLC11A1	ENST00000354352.9	c.*1291_*1294del		3_prime_UTR_variant, NMD_transcript_variant	16/16	1
SLC11A1	ENST00000465984.5	n.2160+25_2160+28del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0820 AC: 12444 AN: 151782 Hom.: 1036 Cov.: 32

Gnomad AFR AF: 0.211

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0774

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0667

Gnomad FIN AF: 0.0226

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0160

Gnomad OTH AF: 0.0728

GnomAD4 exome AF: 0.0297 AC: 36147 AN: 1218308 Hom.: 1568 AF XY: 0.0295 AC XY: 17984 AN XY: 609504

Gnomad4 AFR exome AF: 0.218

Gnomad4 AMR exome AF: 0.108

Gnomad4 ASJ exome AF: 0.0124

Gnomad4 EAS exome AF: 0.116

Gnomad4 SAS exome AF: 0.0544

Gnomad4 FIN exome AF: 0.0196

Gnomad4 NFE exome AF: 0.0155

Gnomad4 OTH exome AF: 0.0442

GnomAD4 genome AF: 0.0820 AC: 12456 AN: 151900 Hom.: 1034 Cov.: 32 AF XY: 0.0825 AC XY: 6126 AN XY: 74278

Gnomad4 AFR AF: 0.210

Gnomad4 AMR AF: 0.0773

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.145

Gnomad4 SAS AF: 0.0659

Gnomad4 FIN AF: 0.0226

Gnomad4 NFE AF: 0.0160

Gnomad4 OTH AF: 0.0720

Alfa AF: 0.0525 Hom.: 70

Bravo AF: 0.0930

Asia WGS AF: 0.116 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs17235416; hg19: chr2-219259813;