chr12-50982036-T-C

Variant names:

• chr12-50982036-T-C
• rs829021
• ENST00000547198.5:c.1630-233A>G

Variant summary

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

The NM_001379446.1(SLC11A2):​c.1717-233A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.908 in 152,214 control chromosomes in the GnomAD database, including 63,086 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 0.91 (63086 hom., cov: 31)
• Consequence: SLC11A2 NM_001379446.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.569
• Publications: 5 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=-0.89).
• 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_001379446.1. 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_001379446.1		c.1717-233A>G		intron	N/A	NP_001366375.1	P49281-4
	SLC11A2	NM_001174126.2		c.1630-233A>G		intron	N/A	NP_001167597.1	A0A0X8GKR4
	SLC11A2	NM_001174127.2		c.1630-233A>G		intron	N/A	NP_001167598.1	A0A0X8GKR4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	ENST00000547198.5	TSL:1	c.1630-233A>G		intron	N/A	ENSP00000446769.1	P49281-1
	SLC11A2	ENST00000546636.5	TSL:1	n.1630-233A>G		intron	N/A	ENSP00000449008.1	P49281-1
	SLC11A2	ENST00000547688.7	TSL:5	c.1717-233A>G		intron	N/A	ENSP00000449200.2	P49281-4

Frequencies

GnomAD3 genomes AF: 0.908 AC: 138132 AN: 152096 Hom.: 63023 Cov.: 31

Gnomad AFR AF: 0.811

Gnomad AMI AF: 0.922

Gnomad AMR AF: 0.939

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.984

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.905

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.921

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

GnomAD4 genome AF: 0.908 AC: 138252 AN: 152214 Hom.: 63086 Cov.: 31 AF XY: 0.913 AC XY: 67915 AN XY: 74420

African (AFR) AF: 0.811 AC: 33664 AN: 41498

American (AMR) AF: 0.940 AC: 14366 AN: 15290

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

East Asian (EAS) AF: 0.984 AC: 5087 AN: 5172

South Asian (SAS) AF: 0.906 AC: 4371 AN: 4826

European-Finnish (FIN) AF: 0.982 AC: 10421 AN: 10608

Middle Eastern (MID) AF: 0.905 AC: 266 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64031 AN: 68030

Other (OTH) AF: 0.922 AC: 1949 AN: 2114

Alfa AF: 0.935 Hom.: 54220

Bravo AF: 0.901

Asia WGS AF: 0.943 AC: 3279 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	7.2
DANN	Benign	0.75
PhyloP100		-0.57
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs829021; hg19: chr12-51375819;