Genetic Variant SLC11A1:n.-45C>T (chr2-218381984-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The ENST00000468221.5(SLC11A1):n.-45C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0557 in 282,344 control chromosomes in the GnomAD database, including 496 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 0.063 ( 312 hom., cov: 31)

Exomes 𝑓: 0.048 ( 184 hom. )

Consequence

SLC11A1
ENST00000468221.5 upstream_gene

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0770

Publications

28 publications found

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]

SLC11A1 Gene-Disease associations (from GenCC):

cystic fibrosis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

SLC11A1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0777 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein
SLC11A1	ENST00000468221.5 link	n.-45C>T	upstream_gene_variant	1
SLC11A1	ENST00000539932.5 link	n.-385C>T	upstream_gene_variant	1	ENSP00000443435.2
SLC11A1	ENST00000465984.5 link	n.-204C>T	upstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0626

AC:

9455

AN:

150988

Hom.:

312

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0801

Gnomad AMI

AF:

0.103

Gnomad AMR

AF:

0.0481

Gnomad ASJ

AF:

0.0569

Gnomad EAS

AF:

0.0420

Gnomad SAS

AF:

0.0563

Gnomad FIN

AF:

0.0468

Gnomad MID

AF:

0.0223

Gnomad NFE

AF:

0.0599

Gnomad OTH

AF:

0.0559

GnomAD4 exome

AF:

0.0478

AC:

6270

AN:

131240

Hom.:

184

Cov.:

AF XY:

0.0469

AC XY:

3226

AN XY:

68788

show subpopulations

African (AFR)

AF:

0.0669

AC:

255

AN:

3812

American (AMR)

AF:

0.0282

AC:

119

AN:

4214

Ashkenazi Jewish (ASJ)

AF:

0.0478

AC:

203

AN:

4246

East Asian (EAS)

AF:

0.0404

AC:

353

AN:

8740

South Asian (SAS)

AF:

0.0452

AC:

521

AN:

11518

European-Finnish (FIN)

AF:

0.0435

AC:

467

AN:

10744

Middle Eastern (MID)

AF:

0.0319

AC:

AN:

596

European-Non Finnish (NFE)

AF:

0.0499

AC:

3974

AN:

79572

Other (OTH)

AF:

0.0460

AC:

359

AN:

7798

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

298

596

893

1191

1489

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.0626

AC:

9457

AN:

151104

Hom.:

312

Cov.:

AF XY:

0.0614

AC XY:

4523

AN XY:

73692

show subpopulations

African (AFR)

AF:

0.0800

AC:

3286

AN:

41086

American (AMR)

AF:

0.0480

AC:

727

AN:

15144

Ashkenazi Jewish (ASJ)

AF:

0.0569

AC:

197

AN:

3462

East Asian (EAS)

AF:

0.0421

AC:

217

AN:

5156

South Asian (SAS)

AF:

0.0557

AC:

267

AN:

4790

European-Finnish (FIN)

AF:

0.0468

AC:

485

AN:

10354

Middle Eastern (MID)

AF:

0.0238

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0599

AC:

4062

AN:

67814

Other (OTH)

AF:

0.0553

AC:

116

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

439

877

1316

1754

2193

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

106

212

318

424

530

<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:

0.0571

Hom.:

422

Bravo

AF:

0.0622

Asia WGS

AF:

0.0470

AC:

165

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

(source)

DANN

Benign

0.40

PhyloP100

0.077

PromoterAI

-0.16

Neutral

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over