12-50998540-G-A

Variant names:

• chr12-50998540-G-A
• rs12227734
• NM_000617.3:c.675+634C>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.675+634C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0713 in 151,982 control chromosomes in the GnomAD database, including 741 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 (741 hom., cov: 32)
• Consequence: SLC11A2 NM_000617.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• Publications: 2 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.27 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.675+634C>T		intron	N/A	NP_000608.1
	SLC11A2	NM_001379446.1		c.762+634C>T		intron	N/A	NP_001366375.1
	SLC11A2	NM_001174125.2		c.762+634C>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.675+634C>T		intron	N/A	ENSP00000262052.5
	SLC11A2	ENST00000394904.9	TSL:1	c.762+634C>T		intron	N/A	ENSP00000378364.3
	SLC11A2	ENST00000547198.5	TSL:1	c.675+634C>T		intron	N/A	ENSP00000446769.1

Frequencies

GnomAD3 genomes AF: 0.0712 AC: 10820 AN: 151864 Hom.: 738 Cov.: 32

Gnomad AFR AF: 0.0626

Gnomad AMI AF: 0.00439

Gnomad AMR AF: 0.187

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.0603

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.0356

Gnomad OTH AF: 0.0711

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

GnomAD4 genome AF: 0.0713 AC: 10829 AN: 151982 Hom.: 741 Cov.: 32 AF XY: 0.0763 AC XY: 5663 AN XY: 74262

African (AFR) AF: 0.0627 AC: 2597 AN: 41452

American (AMR) AF: 0.187 AC: 2847 AN: 15246

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

East Asian (EAS) AF: 0.282 AC: 1455 AN: 5164

South Asian (SAS) AF: 0.0605 AC: 292 AN: 4824

European-Finnish (FIN) AF: 0.0754 AC: 793 AN: 10520

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0356 AC: 2422 AN: 67996

Other (OTH) AF: 0.0699 AC: 147 AN: 2104

Alfa AF: 0.0504 Hom.: 750

Bravo AF: 0.0821

Asia WGS AF: 0.157 AC: 544 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.8
DANN	Benign	0.63
PhyloP100		0.19
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: rs12227734; hg19: chr12-51392323; COSMIC: COSV50373716; COSMIC: COSV50373716;