12-51024025-A-G

Variant names:

• chr12-51024025-A-G
• rs2269683
• NM_000617.3:c.-39+2285T>C

Variant summary

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

The NM_000617.3(SLC11A2):​c.-39+2285T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.071 in 152,198 control chromosomes in the GnomAD database, including 735 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 0.071 (735 hom., cov: 32)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.266
• Publications: 3 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: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet, 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=-0.85).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.268 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	NM_000617.3	MANE Select	c.-39+2285T>C		intron	N/A	NP_000608.1	P49281-2
	SLC11A2	NM_001379446.1		c.49+4152T>C		intron	N/A	NP_001366375.1	P49281-4
	SLC11A2	NM_001174125.2		c.49+4152T>C		intron	N/A	NP_001167596.1	P49281-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	ENST00000262052.9	TSL:1 MANE Select	c.-39+2285T>C		intron	N/A	ENSP00000262052.5	P49281-2
	SLC11A2	ENST00000394904.9	TSL:1	c.49+4152T>C		intron	N/A	ENSP00000378364.3	P49281-3
	SLC11A2	ENST00000547198.5	TSL:1	c.-39+2290T>C		intron	N/A	ENSP00000446769.1	P49281-1

Frequencies

GnomAD3 genomes AF: 0.0710 AC: 10800 AN: 152080 Hom.: 732 Cov.: 32

Gnomad AFR AF: 0.0625

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.186

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.280

Gnomad SAS AF: 0.0601

Gnomad FIN AF: 0.0748

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0355

Gnomad OTH AF: 0.0712

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

GnomAD4 genome AF: 0.0710 AC: 10811 AN: 152198 Hom.: 735 Cov.: 32 AF XY: 0.0759 AC XY: 5648 AN XY: 74416

African (AFR) AF: 0.0625 AC: 2597 AN: 41522

American (AMR) AF: 0.186 AC: 2844 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0746 AC: 259 AN: 3470

East Asian (EAS) AF: 0.280 AC: 1443 AN: 5162

South Asian (SAS) AF: 0.0603 AC: 291 AN: 4822

European-Finnish (FIN) AF: 0.0748 AC: 793 AN: 10606

Middle Eastern (MID) AF: 0.0476 AC: 14 AN: 294

European-Non Finnish (NFE) AF: 0.0355 AC: 2418 AN: 68026

Other (OTH) AF: 0.0700 AC: 148 AN: 2114

Alfa AF: 0.0730 Hom.: 151

Bravo AF: 0.0821

Asia WGS AF: 0.158 AC: 548 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	4.3
DANN	Benign	0.70
PhyloP100		-0.27
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: rs2269683; hg19: chr12-51417808;