Variant 12-50986449-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000617.3(SLC11A2):c.*1876T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 1,283,976 control chromosomes in the GnomAD database, including 208,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21912 hom., cov: 32)

Exomes 𝑓: 0.57 ( 186874 hom. )

Consequence

SLC11A2
NM_000617.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.274

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 12-50986449-A-G is Benign according to our data. Variant chr12-50986449-A-G is described in ClinVar as [Benign]. Clinvar id is 309281.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.616 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3 linkuse as main transcript	c.*1876T>C		3_prime_UTR_variant	16/16	ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9 linkuse as main transcript	c.*1876T>C		3_prime_UTR_variant	16/16	1	NM_000617.3		P49281-2

Frequencies

GnomAD3 genomes

AF:

0.525

AC:

79695

AN:

151848

Hom.:

21905

Cov.:

show subpopulations

Gnomad AFR

AF:

0.382

Gnomad AMI

AF:

0.392

Gnomad AMR

AF:

0.626

Gnomad ASJ

AF:

0.571

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.355

Gnomad FIN

AF:

0.641

Gnomad MID

AF:

0.456

Gnomad NFE

AF:

0.594

Gnomad OTH

AF:

0.538

GnomAD3 exomes

AF:

0.543

AC:

69862

AN:

128744

Hom.:

19871

AF XY:

0.525

AC XY:

37035

AN XY:

70480

show subpopulations

Gnomad AFR exome

AF:

0.376

Gnomad AMR exome

AF:

0.677

Gnomad ASJ exome

AF:

0.580

Gnomad EAS exome

AF:

0.366

Gnomad SAS exome

AF:

0.366

Gnomad FIN exome

AF:

0.641

Gnomad NFE exome

AF:

0.598

Gnomad OTH exome

AF:

0.550

GnomAD4 exome

AF:

0.569

AC:

644075

AN:

1132010

Hom.:

186874

Cov.:

AF XY:

0.562

AC XY:

312148

AN XY:

555408

show subpopulations

Gnomad4 AFR exome

AF:

0.358

Gnomad4 AMR exome

AF:

0.676

Gnomad4 ASJ exome

AF:

0.576

Gnomad4 EAS exome

AF:

0.369

Gnomad4 SAS exome

AF:

0.367

Gnomad4 FIN exome

AF:

0.632

Gnomad4 NFE exome

AF:

0.591

Gnomad4 OTH exome

AF:

0.543

GnomAD4 genome

AF:

0.525

AC:

79731

AN:

151966

Hom.:

21912

Cov.:

AF XY:

0.525

AC XY:

38962

AN XY:

74284

show subpopulations

Gnomad4 AFR

AF:

0.381

Gnomad4 AMR

AF:

0.626

Gnomad4 ASJ

AF:

0.571

Gnomad4 EAS

AF:

0.372

Gnomad4 SAS

AF:

0.354

Gnomad4 FIN

AF:

0.641

Gnomad4 NFE

AF:

0.594

Gnomad4 OTH

AF:

0.539

Alfa

AF:

0.579

Hom.:

52690

Bravo

AF:

0.522

Asia WGS

AF:

0.408

AC:

1416

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

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

-0.82

CADD

Benign

6.4

DANN

Benign

0.66

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over