rs17216086

chr12-50990872-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.25

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]

ACMG classification

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 GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	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	c.1498C>T	p.Arg500Trp	missense_variant	15/16	1	NM_000617.3

Frequencies

GnomAD3 genomes AF: 0.00429 AC: 652 AN: 152064 Hom.: 2 Cov.: 32

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.: 2 AF XY: 0.000819 AC XY: 111 AN XY: 135598

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.: 6 Cov.: 31 AF XY: 0.000333 AC XY: 242 AN XY: 727186

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.: 2 Cov.: 32 AF XY: 0.00422 AC XY: 314 AN XY: 74410

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.: 1

Bravo AF: 0.00463

ESP6500AA AF: 0.0154 AC: 68

ESP6500EA AF: 0.000233 AC: 2

ExAC AF: 0.00142 AC: 172

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.000109

EpiControl AF: 0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Nov 18, 2023

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.44	T
BayesDel_noAF	Benign	-0.39
Cadd	Benign	23
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	D
MetaRNN	Benign	0.0038	T;T;T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-1.0	T
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	T
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	T
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

Other links and lift over

dbSNP: rs17216086; hg19: chr12-51384655;