Genetic Variant SLC11A2:c.309+44A>C (chr12-51005267-T-G) – ACMG Classification: Benign (-20 pts)

Variant summary

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

The NM_000617.3(SLC11A2):c.309+44A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,601,754 control chromosomes in the GnomAD database, including 448,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.74 ( 42228 hom., cov: 32)

Exomes 𝑓: 0.75 ( 406374 hom. )

Consequence

SLC11A2
NM_000617.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.914

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=-0.8).

BP6

Variant 12-51005267-T-G is Benign according to our data. Variant chr12-51005267-T-G is described in ClinVar as [Benign]. Clinvar id is 1332973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A2	NM_000617.3 link	c.309+44A>C		intron_variant	Intron 4 of 15	ENST00000262052.9	NP_000608.1	P49281-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A2	ENST00000262052.9 link	c.309+44A>C		intron_variant	Intron 4 of 15	1	NM_000617.3	ENSP00000262052.5		P49281-2

Frequencies

GnomAD3 genomes

AF:

0.743

AC:

112786

AN:

151896

Hom.:

42200

Cov.:

show subpopulations

Gnomad AFR

AF:

0.674

Gnomad AMI

AF:

0.729

Gnomad AMR

AF:

0.803

Gnomad ASJ

AF:

0.775

Gnomad EAS

AF:

0.870

Gnomad SAS

AF:

0.644

Gnomad FIN

AF:

0.831

Gnomad MID

AF:

0.709

Gnomad NFE

AF:

0.753

Gnomad OTH

AF:

0.741

GnomAD3 exomes

AF:

0.763

AC:

191665

AN:

251096

Hom.:

73874

AF XY:

0.754

AC XY:

102375

AN XY:

135726

show subpopulations

Gnomad AFR exome

AF:

0.672

Gnomad AMR exome

AF:

0.846

Gnomad ASJ exome

AF:

0.779

Gnomad EAS exome

AF:

0.867

Gnomad SAS exome

AF:

0.629

Gnomad FIN exome

AF:

0.823

Gnomad NFE exome

AF:

0.759

Gnomad OTH exome

AF:

0.742

GnomAD4 exome

AF:

0.747

AC:

1082548

AN:

1449740

Hom.:

406374

Cov.:

AF XY:

0.743

AC XY:

536700

AN XY:

721894

show subpopulations

Gnomad4 AFR exome

AF:

0.660

Gnomad4 AMR exome

AF:

0.842

Gnomad4 ASJ exome

AF:

0.778

Gnomad4 EAS exome

AF:

0.877

Gnomad4 SAS exome

AF:

0.631

Gnomad4 FIN exome

AF:

0.819

Gnomad4 NFE exome

AF:

0.747

Gnomad4 OTH exome

AF:

0.739

GnomAD4 genome

AF:

0.742

AC:

112857

AN:

152014

Hom.:

42228

Cov.:

AF XY:

0.747

AC XY:

55531

AN XY:

74308

show subpopulations

Gnomad4 AFR

AF:

0.674

Gnomad4 AMR

AF:

0.802

Gnomad4 ASJ

AF:

0.775

Gnomad4 EAS

AF:

0.870

Gnomad4 SAS

AF:

0.643

Gnomad4 FIN

AF:

0.831

Gnomad4 NFE

AF:

0.753

Gnomad4 OTH

AF:

0.744

Alfa

AF:

0.752

Hom.:

73751

Bravo

AF:

0.741

Asia WGS

AF:

0.772

AC:

2687

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Microcytic anemia with liver iron overload

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.29

DANN

Benign

0.41

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