12-51007630-T-C

Variant names:

• chr12-51007630-T-C
• rs224592
• NM_000617.3:c.183+846A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000617.3(SLC11A2):​c.183+846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 151,600 control chromosomes in the GnomAD database, including 60,644 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.89 (60644 hom., cov: 28)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.634
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.961 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.183+846A>G		intron	N/A	NP_000608.1
	SLC11A2	NM_001379446.1		c.270+846A>G		intron	N/A	NP_001366375.1
	SLC11A2	NM_001174125.2		c.270+846A>G		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.183+846A>G		intron	N/A	ENSP00000262052.5
	SLC11A2	ENST00000394904.9	TSL:1	c.270+846A>G		intron	N/A	ENSP00000378364.3
	SLC11A2	ENST00000547198.5	TSL:1	c.183+846A>G		intron	N/A	ENSP00000446769.1

Frequencies

GnomAD3 genomes AF: 0.890 AC: 134852 AN: 151488 Hom.: 60611 Cov.: 28

Gnomad AFR AF: 0.747

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.907

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.895

Gnomad NFE AF: 0.942

Gnomad OTH AF: 0.909

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.890 AC: 134930 AN: 151600 Hom.: 60644 Cov.: 28 AF XY: 0.895 AC XY: 66287 AN XY: 74078

African (AFR) AF: 0.747 AC: 30753 AN: 41172

American (AMR) AF: 0.930 AC: 14176 AN: 15240

Ashkenazi Jewish (ASJ) AF: 0.938 AC: 3258 AN: 3472

East Asian (EAS) AF: 0.984 AC: 5021 AN: 5102

South Asian (SAS) AF: 0.908 AC: 4351 AN: 4794

European-Finnish (FIN) AF: 0.982 AC: 10378 AN: 10564

Middle Eastern (MID) AF: 0.894 AC: 261 AN: 292

European-Non Finnish (NFE) AF: 0.942 AC: 63981 AN: 67950

Other (OTH) AF: 0.910 AC: 1916 AN: 2106

Alfa AF: 0.907 Hom.: 7710

Bravo AF: 0.879

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.92
DANN	Benign	0.26
PhyloP100		-0.63
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: rs224592; hg19: chr12-51401413;