12-51005267-T-G

Variant names:

• chr12-51005267-T-G
• rs224589
• NM_000617.3:c.309+44A>C

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.309+44A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.746 in 1,601,754 control chromosomes in the GnomAD database, including 448,602 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (42228 hom., cov: 32)
  • Exomes 𝑓: 0.75 (406374 hom.)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.914
• Publications: 47 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=-0.8).
• BP6: Variant 12-51005267-T-G is Benign according to our data. Variant chr12-51005267-T-G is described in ClinVar as Benign. ClinVar VariationId is 1332973.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.848 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000617.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	NM_000617.3	MANE Select	c.309+44A>C		intron	N/A	NP_000608.1
	SLC11A2	NM_001379446.1		c.396+44A>C		intron	N/A	NP_001366375.1
	SLC11A2	NM_001174125.2		c.396+44A>C		intron	N/A	NP_001167596.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	ENST00000262052.9	TSL:1 MANE Select	c.309+44A>C		intron	N/A	ENSP00000262052.5
	SLC11A2	ENST00000394904.9	TSL:1	c.396+44A>C		intron	N/A	ENSP00000378364.3
	SLC11A2	ENST00000547198.5	TSL:1	c.309+44A>C		intron	N/A	ENSP00000446769.1

Frequencies

GnomAD3 genomes AF: 0.743 AC: 112786 AN: 151896 Hom.: 42200 Cov.: 32

Gnomad AFR AF: 0.674

Gnomad AMI AF: 0.729

Gnomad AMR AF: 0.803

Gnomad ASJ AF: 0.775

Gnomad EAS AF: 0.870

Gnomad SAS AF: 0.644

Gnomad FIN AF: 0.831

Gnomad MID AF: 0.709

Gnomad NFE AF: 0.753

Gnomad OTH AF: 0.741

GnomAD2 exomes AF: 0.763 AC: 191665 AN: 251096 AF XY: 0.754

Gnomad AFR exome AF: 0.672

Gnomad AMR exome AF: 0.846

Gnomad ASJ exome AF: 0.779

Gnomad EAS exome AF: 0.867

Gnomad FIN exome AF: 0.823

Gnomad NFE exome AF: 0.759

Gnomad OTH exome AF: 0.742

GnomAD4 exome AF: 0.747 AC: 1082548 AN: 1449740 Hom.: 406374 Cov.: 26 AF XY: 0.743 AC XY: 536700 AN XY: 721894

African (AFR) AF: 0.660 AC: 21935 AN: 33216

American (AMR) AF: 0.842 AC: 37609 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.778 AC: 20252 AN: 26032

East Asian (EAS) AF: 0.877 AC: 34679 AN: 39556

South Asian (SAS) AF: 0.631 AC: 54076 AN: 85702

European-Finnish (FIN) AF: 0.819 AC: 43617 AN: 53264

Middle Eastern (MID) AF: 0.640 AC: 3676 AN: 5740

European-Non Finnish (NFE) AF: 0.747 AC: 822423 AN: 1101606

Other (OTH) AF: 0.739 AC: 44281 AN: 59958

GnomAD4 genome AF: 0.742 AC: 112857 AN: 152014 Hom.: 42228 Cov.: 32 AF XY: 0.747 AC XY: 55531 AN XY: 74308

African (AFR) AF: 0.674 AC: 27907 AN: 41434

American (AMR) AF: 0.802 AC: 12241 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.775 AC: 2687 AN: 3468

East Asian (EAS) AF: 0.870 AC: 4505 AN: 5180

South Asian (SAS) AF: 0.643 AC: 3092 AN: 4806

European-Finnish (FIN) AF: 0.831 AC: 8787 AN: 10578

Middle Eastern (MID) AF: 0.711 AC: 209 AN: 294

European-Non Finnish (NFE) AF: 0.753 AC: 51197 AN: 67976

Other (OTH) AF: 0.744 AC: 1569 AN: 2110

Alfa AF: 0.749 Hom.: 117879

Bravo AF: 0.741

Asia WGS AF: 0.772 AC: 2687 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

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.29
DANN	Benign	0.41
PhyloP100		-0.91
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: rs224589; hg19: chr12-51399050;