12-50987935-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.*390G>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 0.165 in 1,279,300 control chromosomes in the GnomAD database, including 19,273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.17 (2597 hom., cov: 32)
  • Exomes 𝑓: 0.16 (16676 hom.)
• Consequence: SLC11A2 NM_000617.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.576

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=-0.79).
• BP6: Variant 12-50987935-C-T is Benign according to our data. Variant chr12-50987935-C-T is described in ClinVar as [Benign]. Clinvar id is 309299.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.48 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	c.*390G>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.*390G>A		3_prime_UTR_variant	16/16	1	NM_000617.3

Frequencies

GnomAD3 genomes AF: 0.170 AC: 25837 AN: 152014 Hom.: 2597 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.159

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.496

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.189

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.158

Gnomad OTH AF: 0.168

GnomAD3 exomes AF: 0.205 AC: 26110 AN: 127490 Hom.: 3248 AF XY: 0.210 AC XY: 14611 AN XY: 69420

Gnomad AFR exome AF: 0.130

Gnomad AMR exome AF: 0.155

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.501

Gnomad SAS exome AF: 0.262

Gnomad FIN exome AF: 0.185

Gnomad NFE exome AF: 0.155

Gnomad OTH exome AF: 0.186

GnomAD4 exome AF: 0.165 AC: 185774 AN: 1127168 Hom.: 16676 Cov.: 26 AF XY: 0.169 AC XY: 93222 AN XY: 552836

Gnomad4 AFR exome AF: 0.127

Gnomad4 AMR exome AF: 0.155

Gnomad4 ASJ exome AF: 0.205

Gnomad4 EAS exome AF: 0.496

Gnomad4 SAS exome AF: 0.263

Gnomad4 FIN exome AF: 0.182

Gnomad4 NFE exome AF: 0.152

Gnomad4 OTH exome AF: 0.179

GnomAD4 genome AF: 0.170 AC: 25847 AN: 152132 Hom.: 2597 Cov.: 32 AF XY: 0.176 AC XY: 13091 AN XY: 74358

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.159

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.496

Gnomad4 SAS AF: 0.288

Gnomad4 FIN AF: 0.189

Gnomad4 NFE AF: 0.158

Gnomad4 OTH AF: 0.169

Alfa AF: 0.158 Hom.: 2140

Bravo AF: 0.165

Asia WGS AF: 0.356 AC: 1239 AN: 3474

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	-0.79
Cadd	Benign	7.4
Dann	Benign	0.50

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: rs224446; hg19: chr12-51381718;