Variant 12-50990872-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_000617.3(SLC11A2):c.1498C>T(p.Arg500Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000799 in 1,613,912 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 2 hom., cov: 32)

Exomes 𝑓: 0.00044 ( 6 hom. )

Consequence

SLC11A2
NM_000617.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.25

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0038267672).

BP6

Variant 12-50990872-G-A is Benign according to our data. Variant chr12-50990872-G-A is described in ClinVar as [Benign]. Clinvar id is 2047551.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00428 (651/152182) while in subpopulation AFR AF= 0.0147 (608/41496). AF 95% confidence interval is 0.0137. There are 2 homozygotes in gnomad4. There are 314 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3 linkuse as main transcript	c.1498C>T	p.Arg500Trp	missense_variant	15/16	ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9 linkuse as main transcript	c.1498C>T	p.Arg500Trp	missense_variant	15/16	1	NM_000617.3		P49281-2

Frequencies

GnomAD3 genomes

AF:

0.00429

AC:

652

AN:

152064

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0147

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00196

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000118

Gnomad OTH

AF:

0.00240

GnomAD3 exomes

AF:

0.00125

AC:

314

AN:

250886

Hom.:

AF XY:

0.000819

AC XY:

111

AN XY:

135598

show subpopulations

Gnomad AFR exome

AF:

0.0165

Gnomad AMR exome

AF:

0.00104

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000441

Gnomad OTH exome

AF:

0.000979

GnomAD4 exome

AF:

0.000437

AC:

639

AN:

1461730

Hom.:

Cov.:

AF XY:

0.000333

AC XY:

242

AN XY:

727186

show subpopulations

Gnomad4 AFR exome

AF:

0.0136

Gnomad4 AMR exome

AF:

0.00130

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000423

Gnomad4 OTH exome

AF:

0.00123

GnomAD4 genome

AF:

0.00428

AC:

651

AN:

152182

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74410

show subpopulations

Gnomad4 AFR

AF:

0.0147

Gnomad4 AMR

AF:

0.00196

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000118

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00108

Hom.:

Bravo

AF:

0.00463

ESP6500AA

AF:

0.0154

AC:

ESP6500EA

AF:

0.000233

AC:

ExAC

AF:

0.00142

AC:

172

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.44

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

T;T;.;T;.;.;.;.;.;.;.

Eigen

Benign

-0.016

Eigen_PC

Benign

0.087

FATHMM_MKL

Uncertain

0.81

LIST_S2

Uncertain

0.94

.;.;D;D;.;.;.;D;D;D;D

MetaRNN

Benign

0.0038

T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N;.;N;N;N;.;N;.;.;.

MutationTaster

Benign

1.0

N;N;N;N;N;N;N;N

PrimateAI

Benign

0.28

PROVEAN

Benign

-2.4

N;.;.;N;N;.;N;N;N;N;N

REVEL

Benign

0.10

Sift

Uncertain

0.015

D;.;.;D;D;.;D;D;D;D;D

Sift4G

Uncertain

0.020

D;.;.;D;D;.;D;D;D;D;D

Polyphen

0.41

B;B;.;B;P;P;P;P;.;.;P

Vest4

0.25

MVP

0.76

MPC

1.0

ClinPred

0.051

GERP RS

5.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.10

gMVP

0.36

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