rs2279015

Positions:

• chr2-218394547-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000578.4(SLC11A1):​c.1389-85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,462,860 control chromosomes in the GnomAD database, including 127,045 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 0.50 (22171 hom., cov: 33)
  • Exomes 𝑓: 0.39 (104874 hom.)
• Consequence: SLC11A1 NM_000578.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.71

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC11A1	NM_000578.4	c.1389-85G>A		intron_variant		ENST00000233202.11	NP_000569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000233202.11	c.1389-85G>A		intron_variant		1	NM_000578.4	ENSP00000233202.6

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75628 AN: 151974 Hom.: 22123 Cov.: 33

Gnomad AFR AF: 0.828

Gnomad AMI AF: 0.245

Gnomad AMR AF: 0.431

Gnomad ASJ AF: 0.348

Gnomad EAS AF: 0.295

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.323

Gnomad MID AF: 0.418

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.470

GnomAD4 exome AF: 0.392 AC: 513182 AN: 1310768 Hom.: 104874 Cov.: 19 AF XY: 0.387 AC XY: 252017 AN XY: 651464

Gnomad4 AFR exome AF: 0.849

Gnomad4 AMR exome AF: 0.422

Gnomad4 ASJ exome AF: 0.355

Gnomad4 EAS exome AF: 0.305

Gnomad4 SAS exome AF: 0.314

Gnomad4 FIN exome AF: 0.326

Gnomad4 NFE exome AF: 0.388

Gnomad4 OTH exome AF: 0.402

GnomAD4 genome AF: 0.498 AC: 75746 AN: 152092 Hom.: 22171 Cov.: 33 AF XY: 0.491 AC XY: 36528 AN XY: 74352

Gnomad4 AFR AF: 0.828

Gnomad4 AMR AF: 0.432

Gnomad4 ASJ AF: 0.348

Gnomad4 EAS AF: 0.296

Gnomad4 SAS AF: 0.312

Gnomad4 FIN AF: 0.323

Gnomad4 NFE AF: 0.379

Gnomad4 OTH AF: 0.472

Alfa AF: 0.420 Hom.: 3025

Bravo AF: 0.522

Asia WGS AF: 0.358 AC: 1247 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.25
DANN	Benign	0.44

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: rs2279015; hg19: chr2-219259270; COSMIC: COSV51915561; COSMIC: COSV51915561;