chr12-51022737-T-C

Variant names:

• chr12-51022737-T-C
• rs224572
• NM_000617.3:c.-39+3573A>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.-39+3573A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.454 in 152,052 control chromosomes in the GnomAD database, including 16,963 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 0.45 (16963 hom., cov: 32)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.54
• Publications: 12 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=-0.68).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 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.-39+3573A>G		intron	N/A	NP_000608.1
	SLC11A2	NM_001379446.1		c.49+5440A>G		intron	N/A	NP_001366375.1
	SLC11A2	NM_001174125.2		c.49+5440A>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.-39+3573A>G		intron	N/A	ENSP00000262052.5
	SLC11A2	ENST00000394904.9	TSL:1	c.49+5440A>G		intron	N/A	ENSP00000378364.3
	SLC11A2	ENST00000547198.5	TSL:1	c.-39+3578A>G		intron	N/A	ENSP00000446769.1

Frequencies

GnomAD3 genomes AF: 0.454 AC: 68950 AN: 151934 Hom.: 16961 Cov.: 32

Gnomad AFR AF: 0.319

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.440

Gnomad ASJ AF: 0.496

Gnomad EAS AF: 0.0909

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.567

Gnomad MID AF: 0.408

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.467

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

GnomAD4 genome AF: 0.454 AC: 68975 AN: 152052 Hom.: 16963 Cov.: 32 AF XY: 0.449 AC XY: 33338 AN XY: 74316

African (AFR) AF: 0.319 AC: 13209 AN: 41466

American (AMR) AF: 0.440 AC: 6721 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.496 AC: 1722 AN: 3470

East Asian (EAS) AF: 0.0912 AC: 472 AN: 5178

South Asian (SAS) AF: 0.294 AC: 1417 AN: 4822

European-Finnish (FIN) AF: 0.567 AC: 5962 AN: 10524

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

European-Non Finnish (NFE) AF: 0.559 AC: 38009 AN: 67988

Other (OTH) AF: 0.470 AC: 990 AN: 2108

Alfa AF: 0.516 Hom.: 57303

Bravo AF: 0.440

Asia WGS AF: 0.250 AC: 869 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	17
DANN	Benign	0.72
PhyloP100		1.5
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: rs224572; hg19: chr12-51416520; COSMIC: COSV50375650;