rs150909

chr12-50987294-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_000617.3(SLC11A2):c.*1031G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.932 in 1,287,120 control chromosomes in the GnomAD database, including 559,390 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.91 (63322 hom., cov: 32)
  • Exomes 𝑓: 0.93 (496068 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.01

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 (BayesDel_noAF=-0.89).
• BP6: Variant 12-50987294-C-T is Benign according to our data. Variant chr12-50987294-C-T is described in ClinVar as [Benign]. Clinvar id is 309290.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	c.*1031G>A		3_prime_UTR_variant	16/16	ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9	c.*1031G>A		3_prime_UTR_variant	16/16	1	NM_000617.3

Frequencies

GnomAD3 genomes AF: 0.910 AC: 138416 AN: 152114 Hom.: 63256 Cov.: 32

Gnomad AFR AF: 0.815

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.941

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.908

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.922

GnomAD3 exomes AF: 0.938 AC: 122336 AN: 130486 Hom.: 57437 AF XY: 0.935 AC XY: 66594 AN XY: 71222

Gnomad AFR exome AF: 0.810

Gnomad AMR exome AF: 0.959

Gnomad ASJ exome AF: 0.947

Gnomad EAS exome AF: 0.980

Gnomad SAS exome AF: 0.909

Gnomad FIN exome AF: 0.979

Gnomad NFE exome AF: 0.940

Gnomad OTH exome AF: 0.940

GnomAD4 exome AF: 0.935 AC: 1060651 AN: 1134888 Hom.: 496068 Cov.: 56 AF XY: 0.934 AC XY: 520207 AN XY: 556700

Gnomad4 AFR exome AF: 0.797

Gnomad4 AMR exome AF: 0.959

Gnomad4 ASJ exome AF: 0.949

Gnomad4 EAS exome AF: 0.981

Gnomad4 SAS exome AF: 0.909

Gnomad4 FIN exome AF: 0.977

Gnomad4 NFE exome AF: 0.938

Gnomad4 OTH exome AF: 0.931

GnomAD4 genome AF: 0.910 AC: 138539 AN: 152232 Hom.: 63322 Cov.: 32 AF XY: 0.914 AC XY: 68070 AN XY: 74440

Gnomad4 AFR AF: 0.816

Gnomad4 AMR AF: 0.941

Gnomad4 ASJ AF: 0.938

Gnomad4 EAS AF: 0.984

Gnomad4 SAS AF: 0.909

Gnomad4 FIN AF: 0.982

Gnomad4 NFE AF: 0.942

Gnomad4 OTH AF: 0.923

Alfa AF: 0.929 Hom.: 42808

Bravo AF: 0.902

Asia WGS AF: 0.945 AC: 3287 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

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	-0.89
Cadd	Benign	0.11
Dann	Benign	0.71

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: rs150909; hg19: chr12-51381077;