Variant 12-50987294-C-T 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.*1031G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 1,287,120 control chromosomes in the GnomAD database, including 559,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.91 ( 63322 hom., cov: 32)

Exomes 𝑓: 0.93 ( 496068 hom. )

Consequence

SLC11A2
NM_000617.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -2.01

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=-0.89).

BP6

Variant 12-50987294-C-T is Benign according to our data. Variant chr12-50987294-C-T is described in ClinVar as [Benign]. Clinvar id is 309290.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/exons	MANE	UniProt
SLC11A2	NM_000617.3 linkuse as main transcript	c.*1031G>A		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.*1031G>A		3_prime_UTR_variant	16/16	1	NM_000617.3		P49281-2

Frequencies

GnomAD3 genomes

AF:

0.910

AC:

138416

AN:

152114

Hom.:

63256

Cov.:

show subpopulations

Gnomad AFR

AF:

0.815

Gnomad AMI

AF:

0.920

Gnomad AMR

AF:

0.941

Gnomad ASJ

AF:

0.938

Gnomad EAS

AF:

0.984

Gnomad SAS

AF:

0.908

Gnomad FIN

AF:

0.982

Gnomad MID

AF:

0.905

Gnomad NFE

AF:

0.942

Gnomad OTH

AF:

0.922

GnomAD3 exomes

AF:

0.938

AC:

122336

AN:

130486

Hom.:

57437

AF XY:

0.935

AC XY:

66594

AN XY:

71222

show subpopulations

Gnomad AFR exome

AF:

0.810

Gnomad AMR exome

AF:

0.959

Gnomad ASJ exome

AF:

0.947

Gnomad EAS exome

AF:

0.980

Gnomad SAS exome

AF:

0.909

Gnomad FIN exome

AF:

0.979

Gnomad NFE exome

AF:

0.940

Gnomad OTH exome

AF:

0.940

GnomAD4 exome

AF:

0.935

AC:

1060651

AN:

1134888

Hom.:

496068

Cov.:

AF XY:

0.934

AC XY:

520207

AN XY:

556700

show subpopulations

Gnomad4 AFR exome

AF:

0.797

Gnomad4 AMR exome

AF:

0.959

Gnomad4 ASJ exome

AF:

0.949

Gnomad4 EAS exome

AF:

0.981

Gnomad4 SAS exome

AF:

0.909

Gnomad4 FIN exome

AF:

0.977

Gnomad4 NFE exome

AF:

0.938

Gnomad4 OTH exome

AF:

0.931

GnomAD4 genome

AF:

0.910

AC:

138539

AN:

152232

Hom.:

63322

Cov.:

AF XY:

0.914

AC XY:

68070

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.816

Gnomad4 AMR

AF:

0.941

Gnomad4 ASJ

AF:

0.938

Gnomad4 EAS

AF:

0.984

Gnomad4 SAS

AF:

0.909

Gnomad4 FIN

AF:

0.982

Gnomad4 NFE

AF:

0.942

Gnomad4 OTH

AF:

0.923

Alfa

AF:

0.929

Hom.:

42808

Bravo

AF:

0.902

Asia WGS

AF:

0.945

AC:

3287

AN:

3478

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

-0.89

CADD

Benign

0.11

DANN

Benign

0.71

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