chr12-50986965-T-C

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP4_StrongBS1_SupportingBS2

The NM_000617.3(SLC11A2):​c.*1360A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000197 in 1,287,168 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00021 ( 5 hom. )

Consequence

SLC11A2
NM_000617.3 3_prime_UTR

Scores

2

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -1.27
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -9 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.89).
BS1
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.0000919 (14/152340) while in subpopulation SAS AF= 0.00249 (12/4828). AF 95% confidence interval is 0.00143. There are 0 homozygotes in gnomad4. There are 10 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting
BS2
High Homozygotes in GnomAdExome4 at 5 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC11A2NM_000617.3 linkuse as main transcriptc.*1360A>G 3_prime_UTR_variant 16/16 ENST00000262052.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC11A2ENST00000262052.9 linkuse as main transcriptc.*1360A>G 3_prime_UTR_variant 16/161 NM_000617.3 P49281-2

Frequencies

GnomAD3 genomes
AF:
0.0000920
AC:
14
AN:
152222
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0000482
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00248
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000445
AC:
58
AN:
130272
Hom.:
1
AF XY:
0.000534
AC XY:
38
AN XY:
71112
show subpopulations
Gnomad AFR exome
AF:
0.000164
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00250
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000250
GnomAD4 exome
AF:
0.000211
AC:
240
AN:
1134828
Hom.:
5
Cov.:
35
AF XY:
0.000300
AC XY:
167
AN XY:
556682
show subpopulations
Gnomad4 AFR exome
AF:
0.0000411
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00294
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.000363
GnomAD4 genome
AF:
0.0000919
AC:
14
AN:
152340
Hom.:
0
Cov.:
32
AF XY:
0.000134
AC XY:
10
AN XY:
74500
show subpopulations
Gnomad4 AFR
AF:
0.0000481
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00249
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
Asia WGS
AF:
0.00260
AC:
9
AN:
3478

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Microcytic anemia with liver iron overload Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.89
CADD
Benign
6.5
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs573581505; hg19: chr12-51380748; API