chr12-50987294-C-T

Variant names:

• chr12-50987294-C-T
• rs150909
• NM_000617.3:c.*1031G>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.01
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• microcytic anemia with liver iron overload

  Inheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 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 VariationId is 309290.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.962 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A2	NM_000617.3	c.*1031G>A		3_prime_UTR_variant	Exon 16 of 16	ENST00000262052.9	NP_000608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A2	ENST00000262052.9	c.*1031G>A		3_prime_UTR_variant	Exon 16 of 16	1	NM_000617.3	ENSP00000262052.5

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

GnomAD2 exomes AF: 0.938 AC: 122336 AN: 130486 AF XY: 0.935

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 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

African (AFR) AF: 0.797 AC: 19387 AN: 24340

American (AMR) AF: 0.959 AC: 27109 AN: 28258

Ashkenazi Jewish (ASJ) AF: 0.949 AC: 15120 AN: 15938

East Asian (EAS) AF: 0.981 AC: 12598 AN: 12840

South Asian (SAS) AF: 0.909 AC: 69182 AN: 76110

European-Finnish (FIN) AF: 0.977 AC: 12347 AN: 12640

Middle Eastern (MID) AF: 0.905 AC: 2507 AN: 2770

European-Non Finnish (NFE) AF: 0.938 AC: 863920 AN: 920652

Other (OTH) AF: 0.931 AC: 38481 AN: 41340

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

African (AFR) AF: 0.816 AC: 33851 AN: 41496

American (AMR) AF: 0.941 AC: 14379 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3257 AN: 3472

East Asian (EAS) AF: 0.984 AC: 5090 AN: 5172

South Asian (SAS) AF: 0.909 AC: 4383 AN: 4824

European-Finnish (FIN) AF: 0.982 AC: 10438 AN: 10626

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.942 AC: 64087 AN: 68040

Other (OTH) AF: 0.923 AC: 1949 AN: 2112

Alfa AF: 0.932 Hom.: 70547

Bravo AF: 0.902

Asia WGS AF: 0.945 AC: 3287 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs150909; hg19: chr12-51381077;