Variant 12-50987052-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.*1273G>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 0.187 in 1,285,696 control chromosomes in the GnomAD database, including 23,616 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 1871 hom., cov: 32)

Exomes 𝑓: 0.19 ( 21745 hom. )

Consequence

SLC11A2
NM_000617.3 3_prime_UTR

Scores

Clinical Significance

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

Conservation

PhyloP100: -1.40

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=-0.88).

BP6

Variant 12-50987052-C-T is Benign according to our data. Variant chr12-50987052-C-T is described in ClinVar as [Benign]. Clinvar id is 309287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.253 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.*1273G>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.*1273G>A		3_prime_UTR_variant	16/16	1	NM_000617.3		P49281-2

Frequencies

GnomAD3 genomes

AF:

0.147

AC:

22389

AN:

152114

Hom.:

1866

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0719

Gnomad AMI

AF:

0.191

Gnomad AMR

AF:

0.128

Gnomad ASJ

AF:

0.163

Gnomad EAS

AF:

0.115

Gnomad SAS

AF:

0.264

Gnomad FIN

AF:

0.151

Gnomad MID

AF:

0.193

Gnomad NFE

AF:

0.189

Gnomad OTH

AF:

0.166

GnomAD3 exomes

AF:

0.173

AC:

22314

AN:

129312

Hom.:

2207

AF XY:

0.184

AC XY:

12969

AN XY:

70600

show subpopulations

Gnomad AFR exome

AF:

0.0658

Gnomad AMR exome

AF:

0.113

Gnomad ASJ exome

AF:

0.164

Gnomad EAS exome

AF:

0.112

Gnomad SAS exome

AF:

0.275

Gnomad FIN exome

AF:

0.150

Gnomad NFE exome

AF:

0.184

Gnomad OTH exome

AF:

0.194

GnomAD4 exome

AF:

0.192

AC:

218106

AN:

1133464

Hom.:

21745

Cov.:

AF XY:

0.196

AC XY:

108984

AN XY:

555920

show subpopulations

Gnomad4 AFR exome

AF:

0.0651

Gnomad4 AMR exome

AF:

0.114

Gnomad4 ASJ exome

AF:

0.165

Gnomad4 EAS exome

AF:

0.116

Gnomad4 SAS exome

AF:

0.276

Gnomad4 FIN exome

AF:

0.161

Gnomad4 NFE exome

AF:

0.193

Gnomad4 OTH exome

AF:

0.194

GnomAD4 genome

AF:

0.147

AC:

22397

AN:

152232

Hom.:

1871

Cov.:

AF XY:

0.147

AC XY:

10949

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.0718

Gnomad4 AMR

AF:

0.128

Gnomad4 ASJ

AF:

0.163

Gnomad4 EAS

AF:

0.115

Gnomad4 SAS

AF:

0.265

Gnomad4 FIN

AF:

0.151

Gnomad4 NFE

AF:

0.189

Gnomad4 OTH

AF:

0.165

Alfa

AF:

0.178

Hom.:

2093

Bravo

AF:

0.137

Asia WGS

AF:

0.159

AC:

551

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

-0.88

CADD

Benign

0.54

DANN

Benign

0.63

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