rs224454

chr12-50999333-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.607+12G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.163 in 1,610,946 control chromosomes in the GnomAD database, including 24,269 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (2183 hom., cov: 32)
  • Exomes 𝑓: 0.16 (22086 hom.)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.160

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=-0.81).
• BP6: Variant 12-50999333-C-T is Benign according to our data. Variant chr12-50999333-C-T is described in ClinVar as [Benign]. Clinvar id is 309318.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.446 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	c.607+12G>A		intron_variant		ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9	c.607+12G>A		intron_variant		1	NM_000617.3

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22761 AN: 152014 Hom.: 2184 Cov.: 32

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.148

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.461

Gnomad SAS AF: 0.253

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.155

Gnomad OTH AF: 0.151

GnomAD3 exomes AF: 0.185 AC: 46426 AN: 251382 Hom.: 5223 AF XY: 0.189 AC XY: 25624 AN XY: 135862

Gnomad AFR exome AF: 0.0704

Gnomad AMR exome AF: 0.150

Gnomad ASJ exome AF: 0.197

Gnomad EAS exome AF: 0.464

Gnomad SAS exome AF: 0.236

Gnomad FIN exome AF: 0.182

Gnomad NFE exome AF: 0.153

Gnomad OTH exome AF: 0.165

GnomAD4 exome AF: 0.164 AC: 239694 AN: 1458814 Hom.: 22086 Cov.: 31 AF XY: 0.167 AC XY: 121296 AN XY: 725924

Gnomad4 AFR exome AF: 0.0690

Gnomad4 AMR exome AF: 0.150

Gnomad4 ASJ exome AF: 0.200

Gnomad4 EAS exome AF: 0.445

Gnomad4 SAS exome AF: 0.235

Gnomad4 FIN exome AF: 0.181

Gnomad4 NFE exome AF: 0.150

Gnomad4 OTH exome AF: 0.169

GnomAD4 genome AF: 0.150 AC: 22768 AN: 152132 Hom.: 2183 Cov.: 32 AF XY: 0.155 AC XY: 11540 AN XY: 74372

Gnomad4 AFR AF: 0.0716

Gnomad4 AMR AF: 0.148

Gnomad4 ASJ AF: 0.202

Gnomad4 EAS AF: 0.461

Gnomad4 SAS AF: 0.254

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.155

Gnomad4 OTH AF: 0.152

Alfa AF: 0.152 Hom.: 558

Bravo AF: 0.143

Asia WGS AF: 0.320 AC: 1114 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 24, 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	-0.81
Cadd	Benign	11
Dann	Benign	0.39
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs224454; hg19: chr12-51393116; COSMIC: COSV50371028; COSMIC: COSV50371028;