12-50987967-T-C

Variant names:

• chr12-50987967-T-C
• rs2285230
• NM_000617.3:c.*358A>G

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.*358A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,294,320 control chromosomes in the GnomAD database, including 23,821 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1885 hom., cov: 33)
  • Exomes 𝑓: 0.19 (21936 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.738
• Publications: 14 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=-0.9).
• BP6: Variant 12-50987967-T-C is Benign according to our data. Variant chr12-50987967-T-C is described in ClinVar as Benign. ClinVar VariationId is 309300.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.252 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A2	NM_000617.3	c.*358A>G		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.*358A>G		3_prime_UTR_variant	Exon 16 of 16	1	NM_000617.3	ENSP00000262052.5

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22409 AN: 152102 Hom.: 1880 Cov.: 33

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.263

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.188

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.167

GnomAD2 exomes AF: 0.174 AC: 22631 AN: 129904 AF XY: 0.186

Gnomad AFR exome AF: 0.0662

Gnomad AMR exome AF: 0.114

Gnomad ASJ exome AF: 0.167

Gnomad EAS exome AF: 0.112

Gnomad FIN exome AF: 0.151

Gnomad NFE exome AF: 0.185

Gnomad OTH exome AF: 0.197

GnomAD4 exome AF: 0.192 AC: 219789 AN: 1142100 Hom.: 21936 Cov.: 30 AF XY: 0.196 AC XY: 109909 AN XY: 560402

African (AFR) AF: 0.0656 AC: 1622 AN: 24738

American (AMR) AF: 0.115 AC: 3274 AN: 28476

Ashkenazi Jewish (ASJ) AF: 0.166 AC: 2725 AN: 16396

East Asian (EAS) AF: 0.114 AC: 1544 AN: 13504

South Asian (SAS) AF: 0.277 AC: 20998 AN: 75900

European-Finnish (FIN) AF: 0.161 AC: 2107 AN: 13086

Middle Eastern (MID) AF: 0.255 AC: 719 AN: 2820

European-Non Finnish (NFE) AF: 0.193 AC: 178665 AN: 925160

Other (OTH) AF: 0.194 AC: 8135 AN: 42020

GnomAD4 genome AF: 0.147 AC: 22417 AN: 152220 Hom.: 1885 Cov.: 33 AF XY: 0.147 AC XY: 10959 AN XY: 74422

African (AFR) AF: 0.0718 AC: 2985 AN: 41556

American (AMR) AF: 0.128 AC: 1959 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3470

East Asian (EAS) AF: 0.115 AC: 596 AN: 5192

South Asian (SAS) AF: 0.265 AC: 1276 AN: 4824

European-Finnish (FIN) AF: 0.152 AC: 1608 AN: 10586

Middle Eastern (MID) AF: 0.185 AC: 54 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12846 AN: 67994

Other (OTH) AF: 0.165 AC: 350 AN: 2116

Alfa AF: 0.172 Hom.: 3094

Bravo AF: 0.137

Asia WGS AF: 0.159 AC: 551 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 12, 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	-0.90
CADD	Benign	1.6
DANN	Benign	0.44
PhyloP100		-0.74
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: rs2285230; hg19: chr12-51381750;