rs17235416

Variant names:

• chr2-218395090-ATGTG-A
• rs17235416
• NM_000578.4:c.*56_*59delTGTG

Variant summary

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

The NM_000578.4(SLC11A1):​c.*56_*59delTGTG 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
• Publications: 36 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
• Mycobacterium tuberculosis, susceptibility

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000578.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	NM_000578.4	MANE Select	c.*56_*59delTGTG		3_prime_UTR	Exon 15 of 15	NP_000569.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	ENST00000233202.11	TSL:1 MANE Select	c.*56_*59delTGTG		3_prime_UTR	Exon 15 of 15	ENSP00000233202.6	P49279-1
	SLC11A1	ENST00000354352.9	TSL:1	n.*1291_*1294delTGTG		non_coding_transcript_exon	Exon 16 of 16	ENSP00000346320.5	Q9HBK0
	SLC11A1	ENST00000468221.5	TSL:1	n.4836_4839delTGTG		non_coding_transcript_exon	Exon 13 of 13

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

African (AFR) AF: 0.218 AC: 6128 AN: 28160

American (AMR) AF: 0.108 AC: 3871 AN: 36004

Ashkenazi Jewish (ASJ) AF: 0.0124 AC: 298 AN: 24024

East Asian (EAS) AF: 0.116 AC: 4096 AN: 35220

South Asian (SAS) AF: 0.0544 AC: 4164 AN: 76576

European-Finnish (FIN) AF: 0.0196 AC: 825 AN: 42068

Middle Eastern (MID) AF: 0.0431 AC: 195 AN: 4528

European-Non Finnish (NFE) AF: 0.0155 AC: 14263 AN: 919558

Other (OTH) AF: 0.0442 AC: 2307 AN: 52170

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

African (AFR) AF: 0.210 AC: 8677 AN: 41262

American (AMR) AF: 0.0773 AC: 1181 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.0107 AC: 37 AN: 3472

East Asian (EAS) AF: 0.145 AC: 745 AN: 5146

South Asian (SAS) AF: 0.0659 AC: 318 AN: 4824

European-Finnish (FIN) AF: 0.0226 AC: 240 AN: 10606

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0160 AC: 1088 AN: 67992

Other (OTH) AF: 0.0720 AC: 152 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs17235416; hg19: chr2-219259813;