rs161044

Variant names:

• chr12-50988449-T-C
• rs161044
• NM_000617.3:c.1576-14A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000617.3(SLC11A2):​c.1576-14A>G variant causes a 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 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -2.41
• Publications: 11 publications found

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]

SLC11A2 Gene-Disease associations (from GenCC):

• microcytic anemia with liver iron overload

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -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 VariationId is 309307.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A2	NM_000617.3	c.1576-14A>G		intron_variant	Intron 15 of 15	ENST00000262052.9	NP_000608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A2	ENST00000262052.9	c.1576-14A>G		intron_variant	Intron 15 of 15	1	NM_000617.3	ENSP00000262052.5

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

GnomAD2 exomes AF: 0.938 AC: 235291 AN: 250776 AF XY: 0.938

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 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

African (AFR) AF: 0.801 AC: 26794 AN: 33454

American (AMR) AF: 0.960 AC: 42911 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.947 AC: 24739 AN: 26122

East Asian (EAS) AF: 0.983 AC: 39008 AN: 39680

South Asian (SAS) AF: 0.908 AC: 78326 AN: 86246

European-Finnish (FIN) AF: 0.978 AC: 52191 AN: 53384

Middle Eastern (MID) AF: 0.911 AC: 5252 AN: 5764

European-Non Finnish (NFE) AF: 0.939 AC: 1043706 AN: 1111774

Other (OTH) AF: 0.932 AC: 56248 AN: 60376

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

African (AFR) AF: 0.816 AC: 33840 AN: 41496

American (AMR) AF: 0.941 AC: 14395 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3258 AN: 3472

East Asian (EAS) AF: 0.984 AC: 5084 AN: 5166

South Asian (SAS) AF: 0.908 AC: 4379 AN: 4824

European-Finnish (FIN) AF: 0.982 AC: 10435 AN: 10622

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.942 AC: 64073 AN: 68022

Other (OTH) AF: 0.922 AC: 1942 AN: 2106

Alfa AF: 0.929 Hom.: 35104

Bravo AF: 0.902

Asia WGS AF: 0.943 AC: 3281 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:2

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Microcytic anemia with liver iron overload Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.11
DANN	Benign	0.65
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs161044; hg19: chr12-51382232;