rs149411

chr12-50986449-A-G

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.*1876T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,283,976 control chromosomes in the GnomAD database, including 208,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (21912 hom., cov: 32)
  • Exomes 𝑓: 0.57 (186874 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.274

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=-0.82).
• BP6: Variant 12-50986449-A-G is Benign according to our data. Variant chr12-50986449-A-G is described in ClinVar as [Benign]. Clinvar id is 309281.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	c.*1876T>C		3_prime_UTR_variant	16/16	ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9	c.*1876T>C		3_prime_UTR_variant	16/16	1	NM_000617.3

Frequencies

GnomAD3 genomes AF: 0.525 AC: 79695 AN: 151848 Hom.: 21905 Cov.: 32

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.392

Gnomad AMR AF: 0.626

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.372

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.641

Gnomad MID AF: 0.456

Gnomad NFE AF: 0.594

Gnomad OTH AF: 0.538

GnomAD3 exomes AF: 0.543 AC: 69862 AN: 128744 Hom.: 19871 AF XY: 0.525 AC XY: 37035 AN XY: 70480

Gnomad AFR exome AF: 0.376

Gnomad AMR exome AF: 0.677

Gnomad ASJ exome AF: 0.580

Gnomad EAS exome AF: 0.366

Gnomad SAS exome AF: 0.366

Gnomad FIN exome AF: 0.641

Gnomad NFE exome AF: 0.598

Gnomad OTH exome AF: 0.550

GnomAD4 exome AF: 0.569 AC: 644075 AN: 1132010 Hom.: 186874 Cov.: 32 AF XY: 0.562 AC XY: 312148 AN XY: 555408

Gnomad4 AFR exome AF: 0.358

Gnomad4 AMR exome AF: 0.676

Gnomad4 ASJ exome AF: 0.576

Gnomad4 EAS exome AF: 0.369

Gnomad4 SAS exome AF: 0.367

Gnomad4 FIN exome AF: 0.632

Gnomad4 NFE exome AF: 0.591

Gnomad4 OTH exome AF: 0.543

GnomAD4 genome AF: 0.525 AC: 79731 AN: 151966 Hom.: 21912 Cov.: 32 AF XY: 0.525 AC XY: 38962 AN XY: 74284

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.626

Gnomad4 ASJ AF: 0.571

Gnomad4 EAS AF: 0.372

Gnomad4 SAS AF: 0.354

Gnomad4 FIN AF: 0.641

Gnomad4 NFE AF: 0.594

Gnomad4 OTH AF: 0.539

Alfa AF: 0.579 Hom.: 52690

Bravo AF: 0.522

Asia WGS AF: 0.408 AC: 1416 AN: 3474

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 13, 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	-0.82
Cadd	Benign	6.4
Dann	Benign	0.66

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: rs149411; hg19: chr12-51380232;