rs2285230

chr12-50987967-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000617.3(SLC11A2):c.*358A>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 0.187 in 1,294,320 control chromosomes in the GnomAD database, including 23,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.15 (1885 hom., cov: 33)
  • Exomes 𝑓: 0.19 (21936 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.738

Genes affected

SLC11A2 (HGNC:10908): (solute carrier family 11 member 2) This gene encodes a member of the solute carrier family 11 protein family. The product of this gene transports divalent metals and is involved in iron absorption. Mutations in this gene are associated with hypochromic microcytic anemia with iron overload. A related solute carrier family 11 protein gene is located on chromosome 2. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Apr 2010]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 12-50987967-T-C is Benign according to our data. Variant chr12-50987967-T-C is described in ClinVar as [Benign]. Clinvar id is 309300.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	c.*358A>G		3_prime_UTR_variant	16/16	ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9	c.*358A>G		3_prime_UTR_variant	16/16	1	NM_000617.3

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22409 AN: 152102 Hom.: 1880 Cov.: 33

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.167

GnomAD3 exomes AF: 0.174 AC: 22631 AN: 129904 Hom.: 2236 AF XY: 0.186 AC XY: 13154 AN XY: 70848

Gnomad AFR exome AF: 0.0662

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.112

Gnomad SAS exome AF: 0.278

Gnomad FIN exome AF: 0.151

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.192 AC: 219789 AN: 1142100 Hom.: 21936 Cov.: 30 AF XY: 0.196 AC XY: 109909 AN XY: 560402

Gnomad4 AFR exome AF: 0.0656

Gnomad4 AMR exome AF: 0.115

Gnomad4 ASJ exome AF: 0.166

Gnomad4 EAS exome AF: 0.114

Gnomad4 SAS exome AF: 0.277

Gnomad4 FIN exome AF: 0.161

Gnomad4 NFE exome AF: 0.193

Gnomad4 OTH exome AF: 0.194

GnomAD4 genome AF: 0.147 AC: 22417 AN: 152220 Hom.: 1885 Cov.: 33 AF XY: 0.147 AC XY: 10959 AN XY: 74422

Gnomad4 AFR AF: 0.0718

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.163

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.265

Gnomad4 FIN AF: 0.152

Gnomad4 NFE AF: 0.189

Gnomad4 OTH AF: 0.165

Alfa AF: 0.177 Hom.: 2582

Bravo AF: 0.137

Asia WGS AF: 0.159 AC: 551 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Microcytic anemia with liver iron overload Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
Cadd	Benign	1.6
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: rs2285230; hg19: chr12-51381750;