rs17229009

Positions:

• chr2-218395295-AAAAC-A
• chr2-218395295-AAAAC-AAAACAAAC
• chr2-218395295-AAAAC-AAAACAAACAAAC

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000578.4(SLC11A1):​c.*269_*272del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000037 in 432,088 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000040 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000036 (0 hom.)
• Consequence: SLC11A1 NM_000578.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A1	NM_000578.4	c.*269_*272del		3_prime_UTR_variant	15/15	ENST00000233202.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A1	ENST00000233202.11	c.*269_*272del		3_prime_UTR_variant	15/15	1	NM_000578.4	P1
SLC11A1	ENST00000468221.5	n.5049_5052del		non_coding_transcript_exon_variant	13/13	1
SLC11A1	ENST00000354352.9	c.*1504_*1507del		3_prime_UTR_variant, NMD_transcript_variant	16/16	1
SLC11A1	ENST00000465984.5	n.2160+238_2160+241del		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000396 AC: 6 AN: 151506 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000485

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000658

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000443

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000356 AC: 10 AN: 280582 Hom.: 0 AF XY: 0.0000412 AC XY: 6 AN XY: 145794

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000591

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000396 AC: 6 AN: 151506 Hom.: 0 Cov.: 0 AF XY: 0.0000541 AC XY: 4 AN XY: 73970

Gnomad4 AFR AF: 0.0000485

Gnomad4 AMR AF: 0.0000658

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000443

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0000879 Hom.: 221

Bravo AF: 0.0000416

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs17229009; hg19: chr2-219260018;