NM_000578.4:c.*86A>G

Variant names:

• chr2-218395121-A-G
• rs1059823
• NM_000578.4:c.*86A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000578.4(SLC11A1):​c.*86A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,035,212 control chromosomes in the GnomAD database, including 99,893 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 0.51 (22175 hom., cov: 32)
  • Exomes 𝑓: 0.41 (77718 hom.)
• Consequence: SLC11A1 NM_000578.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.445
• Publications: 33 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 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.*86A>G		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.*86A>G		3_prime_UTR	Exon 15 of 15	ENSP00000233202.6	P49279-1
	SLC11A1	ENST00000354352.9	TSL:1	n.*1321A>G		non_coding_transcript_exon	Exon 16 of 16	ENSP00000346320.5	Q9HBK0
	SLC11A1	ENST00000468221.5	TSL:1	n.4866A>G		non_coding_transcript_exon	Exon 13 of 13

Frequencies

GnomAD3 genomes AF: 0.508 AC: 77080 AN: 151834 Hom.: 22128 Cov.: 32

Gnomad AFR AF: 0.799

Gnomad AMI AF: 0.284

Gnomad AMR AF: 0.455

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.304

Gnomad SAS AF: 0.330

Gnomad FIN AF: 0.350

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.406

Gnomad OTH AF: 0.486

GnomAD4 exome AF: 0.413 AC: 364529 AN: 883260 Hom.: 77718 Cov.: 11 AF XY: 0.408 AC XY: 184091 AN XY: 451324

African (AFR) AF: 0.811 AC: 17915 AN: 22096

American (AMR) AF: 0.451 AC: 15038 AN: 33354

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 7825 AN: 20814

East Asian (EAS) AF: 0.313 AC: 10380 AN: 33210

South Asian (SAS) AF: 0.331 AC: 22286 AN: 67254

European-Finnish (FIN) AF: 0.353 AC: 12240 AN: 34692

Middle Eastern (MID) AF: 0.385 AC: 1217 AN: 3164

European-Non Finnish (NFE) AF: 0.415 AC: 260190 AN: 627712

Other (OTH) AF: 0.426 AC: 17438 AN: 40964

GnomAD4 genome AF: 0.508 AC: 77202 AN: 151952 Hom.: 22175 Cov.: 32 AF XY: 0.502 AC XY: 37276 AN XY: 74270

African (AFR) AF: 0.799 AC: 33139 AN: 41464

American (AMR) AF: 0.456 AC: 6957 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1267 AN: 3470

East Asian (EAS) AF: 0.305 AC: 1567 AN: 5136

South Asian (SAS) AF: 0.329 AC: 1585 AN: 4814

European-Finnish (FIN) AF: 0.350 AC: 3697 AN: 10568

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.406 AC: 27577 AN: 67932

Other (OTH) AF: 0.488 AC: 1028 AN: 2106

Alfa AF: 0.439 Hom.: 62426

Bravo AF: 0.530

Asia WGS AF: 0.365 AC: 1272 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.6
DANN	Benign	0.39
PhyloP100		0.45
Mutation Taster		=100/0	polymorphism (auto)

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: rs1059823; hg19: chr2-219259844; COSMIC: COSV51916079; COSMIC: COSV51916079;