Variant chr12-50986004-AT-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BS1_SupportingBS2

The NM_000617.3(SLC11A2):c.*2320del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0081 in 1,155,402 control chromosomes in the GnomAD database, including 71 homozygotes. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0057 ( 11 hom., cov: 32)

Exomes 𝑓: 0.0085 ( 60 hom. )

Consequence

SLC11A2
NM_000617.3 3_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.146

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 Likely_benign. Variant got -5 ACMG points.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00569 (865/151920) while in subpopulation NFE AF= 0.00927 (630/67926). AF 95% confidence interval is 0.00868. There are 11 homozygotes in gnomad4. There are 381 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

BS2

High Homozygotes in GnomAd4 at 11 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3 linkuse as main transcript	c.*2320del		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.*2320del		3_prime_UTR_variant	16/16	1	NM_000617.3		P49281-2

Frequencies

GnomAD3 genomes

AF:

0.00569

AC:

863

AN:

151802

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00186

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00802

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00146

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00927

Gnomad OTH

AF:

0.00432

GnomAD3 exomes

AF:

0.00670

AC:

371

AN:

55394

Hom.:

AF XY:

0.00661

AC XY:

204

AN XY:

30884

show subpopulations

Gnomad AFR exome

AF:

0.00107

Gnomad AMR exome

AF:

0.00680

Gnomad ASJ exome

AF:

0.00312

Gnomad EAS exome

AF:

0.000337

Gnomad SAS exome

AF:

0.00472

Gnomad FIN exome

AF:

0.00134

Gnomad NFE exome

AF:

0.0103

Gnomad OTH exome

AF:

0.00839

GnomAD4 exome

AF:

0.00847

AC:

8495

AN:

1003482

Hom.:

Cov.:

AF XY:

0.00816

AC XY:

3924

AN XY:

480630

show subpopulations

Gnomad4 AFR exome

AF:

0.00156

Gnomad4 AMR exome

AF:

0.00651

Gnomad4 ASJ exome

AF:

0.00235

Gnomad4 EAS exome

AF:

0.000193

Gnomad4 SAS exome

AF:

0.00281

Gnomad4 FIN exome

AF:

0.000917

Gnomad4 NFE exome

AF:

0.00932

Gnomad4 OTH exome

AF:

0.00647

GnomAD4 genome

AF:

0.00569

AC:

865

AN:

151920

Hom.:

Cov.:

AF XY:

0.00513

AC XY:

381

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.00191

Gnomad4 AMR

AF:

0.00801

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00146

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.00927

Gnomad4 OTH

AF:

0.00427

Alfa

AF:

0.00195

Hom.:

Bravo

AF:

0.00599

Asia WGS

AF:

0.00202

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Microcytic anemia with liver iron overload

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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