2-218382988-G-A

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 2P and 7B. PM2BP4_StrongBP6_ModerateBP7

The NM_000578.4(SLC11A1):​c.36G>A​(p.Gly12=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000278 in 1,614,086 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 31)
Exomes 𝑓: 0.00029 ( 0 hom. )

Consequence

SLC11A1
NM_000578.4 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.382
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -5 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
Variant 2-218382988-G-A is Benign according to our data. Variant chr2-218382988-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3025428.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-0.382 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SLC11A1NM_000578.4 linkuse as main transcriptc.36G>A p.Gly12= synonymous_variant 2/15 ENST00000233202.11 NP_000569.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SLC11A1ENST00000233202.11 linkuse as main transcriptc.36G>A p.Gly12= synonymous_variant 2/151 NM_000578.4 ENSP00000233202 P1P49279-1

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152090
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.000169
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000338
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000141
AC:
35
AN:
248902
Hom.:
0
AF XY:
0.000148
AC XY:
20
AN XY:
134742
show subpopulations
Gnomad AFR exome
AF:
0.000185
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000288
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000287
AC:
419
AN:
1461878
Hom.:
0
Cov.:
31
AF XY:
0.000267
AC XY:
194
AN XY:
727240
show subpopulations
Gnomad4 AFR exome
AF:
0.0000597
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000371
Gnomad4 OTH exome
AF:
0.0000662
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152208
Hom.:
0
Cov.:
31
AF XY:
0.000242
AC XY:
18
AN XY:
74408
show subpopulations
Gnomad4 AFR
AF:
0.000169
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000338
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000360
Hom.:
0
Bravo
AF:
0.000174
EpiCase
AF:
0.000273
EpiControl
AF:
0.000237

ClinVar

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

Submissions by phenotype

not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2023SLC11A1: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.79
CADD
Benign
8.2
DANN
Benign
0.54

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

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

Other links and lift over

dbSNP: rs17221910; hg19: chr2-219247711; API