dbSNP rs767436028: SLC11A2:c.*1057C>T (chr12-50987268-G-A) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBS1_Supporting

The NM_000617.3(SLC11A2):c.*1057C>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 0.0000691 in 1,287,196 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000051 ( 1 hom. )

Consequence

SLC11A2
NM_000617.3 3_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0340

Publications

0 publications found

Variant links:

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: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Genomics England PanelApp, ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

SLC11A2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.000204 (31/152308) while in subpopulation AFR AF = 0.000625 (26/41572). AF 95% confidence interval is 0.000438. There are 0 homozygotes in GnomAd4. There are 19 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

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

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC11A2	NM_000617.3	MANE Select	c.*1057C>T	3_prime_UTR	Exon 16 of 16	NP_000608.1	P49281-2
SLC11A2	NM_001174125.2		c.*1057C>T	3_prime_UTR	Exon 16 of 16	NP_001167596.1	P49281-3
SLC11A2	NM_001379455.1		c.*1057C>T	3_prime_UTR	Exon 17 of 17	NP_001366384.1	P49281-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SLC11A2	ENST00000262052.9	TSL:1 MANE Select	c.*1057C>T	3_prime_UTR	Exon 16 of 16	ENSP00000262052.5	P49281-2
SLC11A2	ENST00000394904.9	TSL:1	c.*1057C>T	3_prime_UTR	Exon 16 of 16	ENSP00000378364.3	P49281-3
SLC11A2	ENST00000547198.5	TSL:1	c.1629+1114C>T	intron	N/A	ENSP00000446769.1	P49281-1

Frequencies

GnomAD3 genomes

AF:

0.000197

AC:

AN:

152190

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000603

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.0000767

AC:

AN:

130462

AF XY:

0.0000983

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0000411

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000959

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000603

Gnomad OTH exome

AF:

0.000250

GnomAD4 exome

AF:

0.0000511

AC:

AN:

1134888

Hom.:

Cov.:

AF XY:

0.0000467

AC XY:

AN XY:

556708

show subpopulations

African (AFR)

AF:

0.00119

AC:

AN:

24340

American (AMR)

AF:

0.00

AC:

AN:

28258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15938

East Asian (EAS)

AF:

0.0000779

AC:

AN:

12840

South Asian (SAS)

AF:

0.0000394

AC:

AN:

76110

European-Finnish (FIN)

AF:

0.00

AC:

AN:

12642

Middle Eastern (MID)

AF:

0.000722

AC:

AN:

2770

European-Non Finnish (NFE)

AF:

0.0000174

AC:

AN:

920652

Other (OTH)

AF:

0.000169

AC:

AN:

41338

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000204

AC:

AN:

152308

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

AN XY:

74464

show subpopulations

African (AFR)

AF:

0.000625

AC:

AN:

41572

American (AMR)

AF:

0.000131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000941

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68032

Other (OTH)

AF:

0.000473

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.530

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000174

Hom.:

Bravo

AF:

0.000227

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Microcytic anemia with liver iron overload (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.4

(source)

DANN

Benign

0.73

PhyloP100

-0.034

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over