Variant rs427020 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.34+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,444,066 control chromosomes in the GnomAD database, including 187,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.45 ( 16916 hom., cov: 31)

Exomes 𝑓: 0.50 ( 170122 hom. )

Consequence

SLC11A2
NM_000617.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.860

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=-0.86).

BP6

Variant 12-51010684-C-T is Benign according to our data. Variant chr12-51010684-C-T is described in ClinVar as [Benign]. Clinvar id is 309323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr12-51010684-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC11A2	NM_000617.3 linkuse as main transcript	c.34+11G>A		intron_variant		ENST00000262052.9	NP_000608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC11A2	ENST00000262052.9 linkuse as main transcript	c.34+11G>A		intron_variant		1	NM_000617.3	ENSP00000262052		P49281-2

Frequencies

GnomAD3 genomes

AF:

0.453

AC:

68809

AN:

151780

Hom.:

16915

Cov.:

show subpopulations

Gnomad AFR

AF:

0.317

Gnomad AMI

AF:

0.390

Gnomad AMR

AF:

0.440

Gnomad ASJ

AF:

0.497

Gnomad EAS

AF:

0.0915

Gnomad SAS

AF:

0.294

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.408

Gnomad NFE

AF:

0.559

Gnomad OTH

AF:

0.467

GnomAD3 exomes

AF:

0.451

AC:

111986

AN:

248448

Hom.:

28170

AF XY:

0.452

AC XY:

60673

AN XY:

134216

show subpopulations

Gnomad AFR exome

AF:

0.307

Gnomad AMR exome

AF:

0.376

Gnomad ASJ exome

AF:

0.506

Gnomad EAS exome

AF:

0.0903

Gnomad SAS exome

AF:

0.300

Gnomad FIN exome

AF:

0.567

Gnomad NFE exome

AF:

0.565

Gnomad OTH exome

AF:

0.478

GnomAD4 exome

AF:

0.500

AC:

645710

AN:

1292168

Hom.:

170122

Cov.:

AF XY:

0.496

AC XY:

323362

AN XY:

652036

show subpopulations

Gnomad4 AFR exome

AF:

0.286

Gnomad4 AMR exome

AF:

0.387

Gnomad4 ASJ exome

AF:

0.500

Gnomad4 EAS exome

AF:

0.0885

Gnomad4 SAS exome

AF:

0.301

Gnomad4 FIN exome

AF:

0.570

Gnomad4 NFE exome

AF:

0.545

Gnomad4 OTH exome

AF:

0.470

GnomAD4 genome

AF:

0.453

AC:

68828

AN:

151898

Hom.:

16916

Cov.:

AF XY:

0.448

AC XY:

33264

AN XY:

74236

show subpopulations

Gnomad4 AFR

AF:

0.316

Gnomad4 AMR

AF:

0.439

Gnomad4 ASJ

AF:

0.497

Gnomad4 EAS

AF:

0.0917

Gnomad4 SAS

AF:

0.294

Gnomad4 FIN

AF:

0.567

Gnomad4 NFE

AF:

0.559

Gnomad4 OTH

AF:

0.469

Alfa

AF:

0.506

Hom.:

3733

Bravo

AF:

0.439

Asia WGS

AF:

0.249

AC:

864

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -

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

-0.86

CADD

Benign

1.1

DANN

Benign

0.62

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