12-50999333-C-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.160

Publications

11 publications found

Variant links:

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

SLC11A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SLC11A2	NM_000617.3 link	c.607+12G>A		intron_variant	Intron 7 of 15	ENST00000262052.9	NP_000608.1	P49281-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A2	ENST00000262052.9 link	c.607+12G>A		intron_variant	Intron 7 of 15	1	NM_000617.3	ENSP00000262052.5		P49281-2

Frequencies

GnomAD3 genomes

AF:

0.150

AC:

22761

AN:

152014

Hom.:

2184

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.185

AC:

46426

AN:

251382

AF XY:

0.189

show subpopulations

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 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.:

AF XY:

0.167

AC XY:

121296

AN XY:

725924

show subpopulations

African (AFR)

AF:

0.0690

AC:

2306

AN:

33444

American (AMR)

AF:

0.150

AC:

6710

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.200

AC:

5215

AN:

26122

East Asian (EAS)

AF:

0.445

AC:

17650

AN:

39676

South Asian (SAS)

AF:

0.235

AC:

20212

AN:

86178

European-Finnish (FIN)

AF:

0.181

AC:

9656

AN:

53414

Middle Eastern (MID)

AF:

0.151

AC:

872

AN:

5762

European-Non Finnish (NFE)

AF:

0.150

AC:

166866

AN:

1109224

Other (OTH)

AF:

0.169

AC:

10207

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

9702

19403

29105

38806

48508

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6146

12292

18438

24584

30730

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.150

AC:

22768

AN:

152132

Hom.:

2183

Cov.:

AF XY:

0.155

AC XY:

11540

AN XY:

74372

show subpopulations

African (AFR)

AF:

0.0716

AC:

2970

AN:

41494

American (AMR)

AF:

0.148

AC:

2256

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.202

AC:

700

AN:

3472

East Asian (EAS)

AF:

0.461

AC:

2386

AN:

5174

South Asian (SAS)

AF:

0.254

AC:

1223

AN:

4818

European-Finnish (FIN)

AF:

0.188

AC:

1986

AN:

10576

Middle Eastern (MID)

AF:

0.214

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.155

AC:

10561

AN:

68002

Other (OTH)

AF:

0.152

AC:

321

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

968

1936

2904

3872

4840

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

254

508

762

1016

1270

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.151

Hom.:

561

Bravo

AF:

0.143

Asia WGS

AF:

0.320

AC:

1114

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Microcytic anemia with liver iron overload

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Benign

0.39

PhyloP100

0.16

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over