2-218395295-AAAAC-AAAACAAAC

Variant names:

• chr2-218395295-A-AAAAC
• rs17229009
• NM_000578.4:c.*269_*272dupAAAC

Variant summary

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

The NM_000578.4(SLC11A1):​c.*269_*272dupAAAC variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.36 (10119 hom., cov: 0)
  • Exomes 𝑓: 0.29 (13213 hom.)
• Consequence: SLC11A1 NM_000578.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.11
• Publications: 2 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 = 0.389 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.*269_*272dupAAAC		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.*269_*272dupAAAC		3_prime_UTR	Exon 15 of 15	ENSP00000233202.6	P49279-1
	SLC11A1	ENST00000354352.9	TSL:1	n.*1504_*1507dupAAAC		non_coding_transcript_exon	Exon 16 of 16	ENSP00000346320.5	Q9HBK0
	SLC11A1	ENST00000468221.5	TSL:1	n.5049_5052dupAAAC		non_coding_transcript_exon	Exon 13 of 13

Frequencies

GnomAD3 genomes AF: 0.365 AC: 55192 AN: 151390 Hom.: 10107 Cov.: 0

Gnomad AFR AF: 0.395

Gnomad AMI AF: 0.239

Gnomad AMR AF: 0.379

Gnomad ASJ AF: 0.320

Gnomad EAS AF: 0.258

Gnomad SAS AF: 0.270

Gnomad FIN AF: 0.342

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.366

GnomAD4 exome AF: 0.288 AC: 80452 AN: 279464 Hom.: 13213 Cov.: 0 AF XY: 0.282 AC XY: 40882 AN XY: 145218

African (AFR) AF: 0.339 AC: 2983 AN: 8812

American (AMR) AF: 0.329 AC: 3417 AN: 10380

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 2479 AN: 9176

East Asian (EAS) AF: 0.186 AC: 3939 AN: 21176

South Asian (SAS) AF: 0.225 AC: 5657 AN: 25132

European-Finnish (FIN) AF: 0.264 AC: 4763 AN: 18032

Middle Eastern (MID) AF: 0.281 AC: 375 AN: 1336

European-Non Finnish (NFE) AF: 0.307 AC: 51712 AN: 168568

Other (OTH) AF: 0.304 AC: 5127 AN: 16852

GnomAD4 genome AF: 0.365 AC: 55244 AN: 151510 Hom.: 10119 Cov.: 0 AF XY: 0.363 AC XY: 26847 AN XY: 74032

African (AFR) AF: 0.394 AC: 16279 AN: 41298

American (AMR) AF: 0.379 AC: 5768 AN: 15202

Ashkenazi Jewish (ASJ) AF: 0.320 AC: 1110 AN: 3464

East Asian (EAS) AF: 0.259 AC: 1334 AN: 5152

South Asian (SAS) AF: 0.270 AC: 1297 AN: 4812

European-Finnish (FIN) AF: 0.342 AC: 3596 AN: 10522

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24750 AN: 67754

Other (OTH) AF: 0.369 AC: 777 AN: 2104

Alfa AF: 0.124 Hom.: 221

Asia WGS AF: 0.294 AC: 1021 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		2.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs17229009;

hg19: chr2-219260018;