rs161044

chr12-50988449-T-C

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.1576-14A>G variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.934 in 1,613,720 control chromosomes in the GnomAD database, including 705,237 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.91 (63309 hom., cov: 30)
  • Exomes 𝑓: 0.94 (641928 hom.)
• Consequence: SLC11A2 NM_000617.3 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.41

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 12-50988449-T-C is Benign according to our data. Variant chr12-50988449-T-C is described in ClinVar as [Benign]. Clinvar id is 309307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-50988449-T-C is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	c.1576-14A>G		splice_polypyrimidine_tract_variant, intron_variant		ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9	c.1576-14A>G		splice_polypyrimidine_tract_variant, intron_variant		1	NM_000617.3

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138392 AN: 152100 Hom.: 63247 Cov.: 30

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.940

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.921

GnomAD3 exomes AF: 0.938 AC: 235291 AN: 250776 Hom.: 110572 AF XY: 0.938 AC XY: 127064 AN XY: 135522

Gnomad AFR exome AF: 0.809

Gnomad AMR exome AF: 0.961

Gnomad ASJ exome AF: 0.947

Gnomad EAS exome AF: 0.981

Gnomad SAS exome AF: 0.908

Gnomad FIN exome AF: 0.980

Gnomad NFE exome AF: 0.942

Gnomad OTH exome AF: 0.941

GnomAD4 exome AF: 0.937 AC: 1369175 AN: 1461502 Hom.: 641928 Cov.: 45 AF XY: 0.937 AC XY: 681069 AN XY: 727064

Gnomad4 AFR exome AF: 0.801

Gnomad4 AMR exome AF: 0.960

Gnomad4 ASJ exome AF: 0.947

Gnomad4 EAS exome AF: 0.983

Gnomad4 SAS exome AF: 0.908

Gnomad4 FIN exome AF: 0.978

Gnomad4 NFE exome AF: 0.939

Gnomad4 OTH exome AF: 0.932

GnomAD4 genome AF: 0.910 AC: 138511 AN: 152218 Hom.: 63309 Cov.: 30 AF XY: 0.914 AC XY: 68066 AN XY: 74448

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.941

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.984

Gnomad4 SAS AF: 0.908

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.942

Gnomad4 OTH AF: 0.922

Alfa AF: 0.923 Hom.: 21537

Bravo AF: 0.902

Asia WGS AF: 0.943 AC: 3281 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Microcytic anemia with liver iron overload Benign:2

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. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.11
Dann	Benign	0.65

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: rs161044; hg19: chr12-51382232;