rs12227734

Positions:

• chr12-50998540-G-A
• chr12-50998540-G-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A2	NM_000617.3	c.675+634C>T		intron_variant		ENST00000262052.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A2	ENST00000262052.9	c.675+634C>T		intron_variant		1	NM_000617.3

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

Gnomad4 AFR AF: 0.0627

Gnomad4 AMR AF: 0.187

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.282

Gnomad4 SAS AF: 0.0605

Gnomad4 FIN AF: 0.0754

Gnomad4 NFE AF: 0.0356

Gnomad4 OTH AF: 0.0699

Alfa AF: 0.0453 Hom.: 134

Bravo AF: 0.0821

Asia WGS AF: 0.157 AC: 544 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.8
DANN	Benign	0.63

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

Publications

LitVar

Other links and lift over

dbSNP: rs12227734; hg19: chr12-51392323; COSMIC: COSV50373716; COSMIC: COSV50373716;