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rs7576974

chr2-218383067-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_ModerateBP6_ModerateBP7BA1

The NM_000578.4(SLC11A1):c.115C>T(p.Leu39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,613,940 control chromosomes in the GnomAD database, including 932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.043 ( 479 hom., cov: 31)
Exomes 𝑓: 0.0066 ( 453 hom. )

Consequence

SLC11A1
NM_000578.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.133
Variant links:
Genes affected
SLC11A1 (HGNC:10907): (solute carrier family 11 member 1) This gene is a member of the solute carrier family 11 (proton-coupled divalent metal ion transporters) family and encodes a multi-pass membrane protein. The protein functions as a divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. Mutations in this gene have been associated with susceptibility to infectious diseases such as tuberculosis and leprosy, and inflammatory diseases such as rheumatoid arthritis and Crohn disease. Alternatively spliced variants that encode different protein isoforms have been described but the full-length nature of only one has been determined. [provided by RefSeq, Jul 2008]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.42).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-218383067-C-T is Benign according to our data. Variant chr2-218383067-C-T is described in ClinVar as [Benign]. Clinvar id is 3055747.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.133 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
SLC11A1NM_000578.4 linkuse as main transcriptc.115C>T p.Leu39= synonymous_variant 2/15 ENST00000233202.11

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
SLC11A1ENST00000233202.11 linkuse as main transcriptc.115C>T p.Leu39= synonymous_variant 2/151 NM_000578.4 P1P49279-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0431
AC:
6554
AN:
152072
Hom.:
479
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.141
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0227
Gnomad ASJ
AF:
0.0161
Gnomad EAS
AF:
0.00483
Gnomad SAS
AF:
0.0178
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0475
Gnomad NFE
AF:
0.00150
Gnomad OTH
AF:
0.0349
GnomAD3 exomes
AF:
0.0152
AC:
3771
AN:
248498
Hom.:
180
AF XY:
0.0122
AC XY:
1637
AN XY:
134568
show subpopulations
Gnomad AFR exome
AF:
0.149
Gnomad AMR exome
AF:
0.0110
Gnomad ASJ exome
AF:
0.0154
Gnomad EAS exome
AF:
0.00577
Gnomad SAS exome
AF:
0.0164
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00131
Gnomad OTH exome
AF:
0.0119
GnomAD4 exome
AF:
0.00662
AC:
9674
AN:
1461750
Hom.:
453
Cov.:
31
AF XY:
0.00636
AC XY:
4625
AN XY:
727164
show subpopulations
Gnomad4 AFR exome
AF:
0.154
Gnomad4 AMR exome
AF:
0.0119
Gnomad4 ASJ exome
AF:
0.0160
Gnomad4 EAS exome
AF:
0.00539
Gnomad4 SAS exome
AF:
0.0152
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000934
Gnomad4 OTH exome
AF:
0.0146
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0432
AC:
6581
AN:
152190
Hom.:
479
Cov.:
31
AF XY:
0.0416
AC XY:
3093
AN XY:
74426
show subpopulations
Gnomad4 AFR
AF:
0.142
Gnomad4 AMR
AF:
0.0226
Gnomad4 ASJ
AF:
0.0161
Gnomad4 EAS
AF:
0.00484
Gnomad4 SAS
AF:
0.0178
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00150
Gnomad4 OTH
AF:
0.0369
Alfa
AF:
0.0196
Hom.:
131
Bravo
AF:
0.0478
Asia WGS
AF:
0.0340
AC:
118
AN:
3478
EpiCase
AF:
0.00191
EpiControl
AF:
0.00237

ClinVar

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

Submissions by phenotype

SLC11A1-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJan 28, 2020This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.42
Cadd
Benign
9.0
Dann
Benign
0.73

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.080
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: rs7576974; hg19: chr2-219247790; API