rs427020

chr12-51010684-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000617.3(SLC11A2):c.34+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,444,066 control chromosomes in the GnomAD database, including 187,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16916 hom., cov: 31)
  • Exomes 𝑓: 0.50 (170122 hom.)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.860

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 12-51010684-C-T is Benign according to our data. Variant chr12-51010684-C-T is described in ClinVar as [Benign]. Clinvar id is 309323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-51010684-C-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	c.34+11G>A		intron_variant		ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9	c.34+11G>A		intron_variant		1	NM_000617.3

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68809 AN: 151780 Hom.: 16915 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.0915

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.467

GnomAD3 exomes AF: 0.451 AC: 111986 AN: 248448 Hom.: 28170 AF XY: 0.452 AC XY: 60673 AN XY: 134216

Gnomad AFR exome AF: 0.307

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.506

Gnomad EAS exome AF: 0.0903

Gnomad SAS exome AF: 0.300

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.565

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.500 AC: 645710 AN: 1292168 Hom.: 170122 Cov.: 19 AF XY: 0.496 AC XY: 323362 AN XY: 652036

Gnomad4 AFR exome AF: 0.286

Gnomad4 AMR exome AF: 0.387

Gnomad4 ASJ exome AF: 0.500

Gnomad4 EAS exome AF: 0.0885

Gnomad4 SAS exome AF: 0.301

Gnomad4 FIN exome AF: 0.570

Gnomad4 NFE exome AF: 0.545

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.453 AC: 68828 AN: 151898 Hom.: 16916 Cov.: 31 AF XY: 0.448 AC XY: 33264 AN XY: 74236

Gnomad4 AFR AF: 0.316

Gnomad4 AMR AF: 0.439

Gnomad4 ASJ AF: 0.497

Gnomad4 EAS AF: 0.0917

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.567

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.469

Alfa AF: 0.506 Hom.: 3733

Bravo AF: 0.439

Asia WGS AF: 0.249 AC: 864 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

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	-0.86
Cadd	Benign	1.1
Dann	Benign	0.62

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: rs427020; hg19: chr12-51404467;