12-50981283-G-A

Variant names:

• chr12-50981283-G-A
• rs706804
• ENST00000547198.5:c.*443C>T

Variant summary

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

The ENST00000547198.5(SLC11A2):​c.*443C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.881 in 152,930 control chromosomes in the GnomAD database, including 60,119 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 0.88 (59793 hom., cov: 31)
  • Exomes 𝑓: 0.95 (326 hom.)
• Consequence: SLC11A2 ENST00000547198.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0950
• Publications: 4 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=-0.9).
• 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: ENST00000547198.5. 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	NR_183177.1		n.2499C>T		non_coding_transcript_exon	Exon 17 of 17
	SLC11A2	NR_183178.1		n.2504C>T		non_coding_transcript_exon	Exon 17 of 17
	SLC11A2	NM_001379446.1		c.*443C>T		3_prime_UTR	Exon 17 of 17	NP_001366375.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A2	ENST00000547198.5	TSL:1	c.*443C>T		3_prime_UTR	Exon 17 of 17	ENSP00000446769.1
	SLC11A2	ENST00000546636.5	TSL:1	n.*87+356C>T		intron	N/A	ENSP00000449008.1
	SLC11A2	ENST00000547688.7	TSL:5	c.*443C>T		3_prime_UTR	Exon 17 of 17	ENSP00000449200.2

Frequencies

GnomAD3 genomes AF: 0.880 AC: 133866 AN: 152092 Hom.: 59732 Cov.: 31

Gnomad AFR AF: 0.713

Gnomad AMI AF: 0.920

Gnomad AMR AF: 0.930

Gnomad ASJ AF: 0.938

Gnomad EAS AF: 0.983

Gnomad SAS AF: 0.905

Gnomad FIN AF: 0.982

Gnomad MID AF: 0.899

Gnomad NFE AF: 0.941

Gnomad OTH AF: 0.901

GnomAD4 exome AF: 0.950 AC: 684 AN: 720 Hom.: 326 Cov.: 0 AF XY: 0.958 AC XY: 299 AN XY: 312

African (AFR) AF: 0.625 AC: 5 AN: 8

American (AMR) AF: 0.967 AC: 89 AN: 92

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 4 AN: 6

East Asian (EAS) AF: 1.00 AC: 16 AN: 16

South Asian (SAS) AF: 0.962 AC: 50 AN: 52

European-Finnish (FIN) AF: 1.00 AC: 24 AN: 24

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.953 AC: 471 AN: 494

Other (OTH) AF: 0.893 AC: 25 AN: 28

GnomAD4 genome AF: 0.880 AC: 133982 AN: 152210 Hom.: 59793 Cov.: 31 AF XY: 0.885 AC XY: 65897 AN XY: 74428

African (AFR) AF: 0.713 AC: 29565 AN: 41460

American (AMR) AF: 0.931 AC: 14237 AN: 15296

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

East Asian (EAS) AF: 0.983 AC: 5105 AN: 5192

South Asian (SAS) AF: 0.906 AC: 4375 AN: 4830

European-Finnish (FIN) AF: 0.982 AC: 10422 AN: 10610

Middle Eastern (MID) AF: 0.898 AC: 264 AN: 294

European-Non Finnish (NFE) AF: 0.941 AC: 64012 AN: 68032

Other (OTH) AF: 0.902 AC: 1905 AN: 2112

Alfa AF: 0.897 Hom.: 8907

Bravo AF: 0.868

Asia WGS AF: 0.938 AC: 3260 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	3.3
DANN	Benign	0.42
PhyloP100		-0.095
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: rs706804; hg19: chr12-51375066;