rs1005559

Variant names:

• chr12-51020449-T-A
• rs1005559
• NM_000617.3:c.-39+5861A>T

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+5861A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.147 in 152,180 control chromosomes in the GnomAD database, including 1,872 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 0.15 (1872 hom., cov: 31)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 6 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.251 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+5861A>T		intron	N/A	NP_000608.1
	SLC11A2	NM_001379446.1		c.49+7728A>T		intron	N/A	NP_001366375.1
	SLC11A2	NM_001174125.2		c.49+7728A>T		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+5861A>T		intron	N/A	ENSP00000262052.5
	SLC11A2	ENST00000394904.9	TSL:1	c.49+7728A>T		intron	N/A	ENSP00000378364.3
	SLC11A2	ENST00000547198.5	TSL:1	c.-39+5866A>T		intron	N/A	ENSP00000446769.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 22368 AN: 152062 Hom.: 1867 Cov.: 31

Gnomad AFR AF: 0.0720

Gnomad AMI AF: 0.193

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.163

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.262

Gnomad FIN AF: 0.151

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.147 AC: 22376 AN: 152180 Hom.: 1872 Cov.: 31 AF XY: 0.147 AC XY: 10927 AN XY: 74394

African (AFR) AF: 0.0719 AC: 2986 AN: 41540

American (AMR) AF: 0.128 AC: 1959 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.163 AC: 567 AN: 3470

East Asian (EAS) AF: 0.115 AC: 598 AN: 5190

South Asian (SAS) AF: 0.263 AC: 1269 AN: 4820

European-Finnish (FIN) AF: 0.151 AC: 1597 AN: 10578

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.189 AC: 12819 AN: 67984

Other (OTH) AF: 0.165 AC: 349 AN: 2114

Alfa AF: 0.160 Hom.: 265

Bravo AF: 0.137

Asia WGS AF: 0.159 AC: 551 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	0.36
DANN	Benign	0.51
PhyloP100		-1.1
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: rs1005559; hg19: chr12-51414232;