Genetic Variant SLC11A2:c.1197+63C>T (chr12-50992747-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000617.3(SLC11A2):c.1197+63C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.54 ( 19999 hom., cov: 17)

Exomes 𝑓: 0.45 ( 44083 hom. )

Failed GnomAD Quality Control

Consequence

SLC11A2
NM_000617.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.956

Publications

1 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.98).

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.583 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A2	NM_000617.3 link	c.1197+63C>T		intron_variant	Intron 12 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.1197+63C>T		intron_variant	Intron 12 of 15	1	NM_000617.3	ENSP00000262052.5		P49281-2

Frequencies

GnomAD3 genomes

AF:

0.542

AC:

68151

AN:

125770

Hom.:

19995

Cov.:

show subpopulations

Gnomad AFR

AF:

0.506

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.587

Gnomad ASJ

AF:

0.569

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.362

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.467

Gnomad NFE

AF:

0.588

Gnomad OTH

AF:

0.549

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.448

AC:

356742

AN:

797078

Hom.:

44083

AF XY:

0.453

AC XY:

180524

AN XY:

398770

show subpopulations

African (AFR)

AF:

0.432

AC:

7258

AN:

16796

American (AMR)

AF:

0.563

AC:

11015

AN:

19554

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

6448

AN:

13552

East Asian (EAS)

AF:

0.351

AC:

8540

AN:

24354

South Asian (SAS)

AF:

0.456

AC:

20368

AN:

44668

European-Finnish (FIN)

AF:

0.533

AC:

12230

AN:

22954

Middle Eastern (MID)

AF:

0.420

AC:

968

AN:

2304

European-Non Finnish (NFE)

AF:

0.443

AC:

274681

AN:

619410

Other (OTH)

AF:

0.455

AC:

15234

AN:

33486

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

8387

16774

25162

33549

41936

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8488

16976

25464

33952

42440

<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:

0.542

AC:

68150

AN:

125768

Hom.:

19999

Cov.:

AF XY:

0.529

AC XY:

31103

AN XY:

58814

show subpopulations

African (AFR)

AF:

0.506

AC:

16772

AN:

33162

American (AMR)

AF:

0.586

AC:

6359

AN:

10846

Ashkenazi Jewish (ASJ)

AF:

0.569

AC:

1842

AN:

3236

East Asian (EAS)

AF:

0.348

AC:

1593

AN:

4578

South Asian (SAS)

AF:

0.361

AC:

1474

AN:

4086

European-Finnish (FIN)

AF:

0.439

AC:

2098

AN:

4776

Middle Eastern (MID)

AF:

0.470

AC:

109

AN:

232

European-Non Finnish (NFE)

AF:

0.588

AC:

36618

AN:

62252

Other (OTH)

AF:

0.548

AC:

942

AN:

1720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.451

Heterozygous variant carriers

966

1932

2897

3863

4829

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

580

1160

1740

2320

2900

<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:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.98

CADD

Benign

0.48

(source)

DANN

Benign

0.51

PhyloP100

-0.96

Mutation Taster

=12/88

disease causing (long InDel)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over