rs427020

Variant names:

• chr12-51010684-C-T
• rs427020
• NM_000617.3:c.34+11G>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.34+11G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.495 in 1,444,066 control chromosomes in the GnomAD database, including 187,038 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.45 (16916 hom., cov: 31)
  • Exomes 𝑓: 0.50 (170122 hom.)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.860
• Publications: 13 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=-0.86).
• BP6: Variant 12-51010684-C-T is Benign according to our data. Variant chr12-51010684-C-T is described in ClinVar as Benign. ClinVar VariationId is 309323.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A2	NM_000617.3	c.34+11G>A		intron_variant	Intron 2 of 15	ENST00000262052.9	NP_000608.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A2	ENST00000262052.9	c.34+11G>A		intron_variant	Intron 2 of 15	1	NM_000617.3	ENSP00000262052.5

Frequencies

GnomAD3 genomes AF: 0.453 AC: 68809 AN: 151780 Hom.: 16915 Cov.: 31

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.390

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.497

Gnomad EAS AF: 0.0915

Gnomad SAS AF: 0.294

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.467

GnomAD2 exomes AF: 0.451 AC: 111986 AN: 248448 AF XY: 0.452

Gnomad AFR exome AF: 0.307

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.506

Gnomad EAS exome AF: 0.0903

Gnomad FIN exome AF: 0.567

Gnomad NFE exome AF: 0.565

Gnomad OTH exome AF: 0.478

GnomAD4 exome AF: 0.500 AC: 645710 AN: 1292168 Hom.: 170122 Cov.: 19 AF XY: 0.496 AC XY: 323362 AN XY: 652036

African (AFR) AF: 0.286 AC: 8834 AN: 30902

American (AMR) AF: 0.387 AC: 17087 AN: 44170

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 12539 AN: 25084

East Asian (EAS) AF: 0.0885 AC: 3472 AN: 39216

South Asian (SAS) AF: 0.301 AC: 25020 AN: 83112

European-Finnish (FIN) AF: 0.570 AC: 30286 AN: 53128

Middle Eastern (MID) AF: 0.363 AC: 2001 AN: 5518

European-Non Finnish (NFE) AF: 0.545 AC: 520652 AN: 956138

Other (OTH) AF: 0.470 AC: 25819 AN: 54900

GnomAD4 genome AF: 0.453 AC: 68828 AN: 151898 Hom.: 16916 Cov.: 31 AF XY: 0.448 AC XY: 33264 AN XY: 74236

African (AFR) AF: 0.316 AC: 13081 AN: 41384

American (AMR) AF: 0.439 AC: 6697 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.497 AC: 1721 AN: 3466

East Asian (EAS) AF: 0.0917 AC: 474 AN: 5170

South Asian (SAS) AF: 0.294 AC: 1415 AN: 4818

European-Finnish (FIN) AF: 0.567 AC: 5973 AN: 10534

Middle Eastern (MID) AF: 0.405 AC: 119 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 38005 AN: 67972

Other (OTH) AF: 0.469 AC: 991 AN: 2112

Alfa AF: 0.506 Hom.: 3733

Bravo AF: 0.439

Asia WGS AF: 0.249 AC: 864 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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	-0.86
CADD	Benign	1.1
DANN	Benign	0.62
PhyloP100		-0.86
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: rs427020; hg19: chr12-51404467;