Genetic Variant SLC11A1:p.Phe66Phe (chr2-218384290-C-T) – ACMG Classification: Benign (-11 pts)

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_ModerateBP7BA1

The NM_000578.4(SLC11A1):c.198C>T(p.Phe66Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.255 in 1,607,394 control chromosomes in the GnomAD database, including 54,268 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.23 ( 4358 hom., cov: 32)

Exomes 𝑓: 0.26 ( 49910 hom. )

Consequence

SLC11A1
NM_000578.4 synonymous

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: 0.710

Publications

49 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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.27).

BP7

Synonymous conserved (PhyloP=0.71 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A1	NM_000578.4 link	c.198C>T	p.Phe66Phe	synonymous_variant	Exon 3 of 15	ENST00000233202.11	NP_000569.3	P49279-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000233202.11 link	c.198C>T	p.Phe66Phe	synonymous_variant	Exon 3 of 15	1	NM_000578.4	ENSP00000233202.6		P49279-1

Frequencies

GnomAD3 genomes

AF:

0.232

AC:

35352

AN:

152094

Hom.:

4355

Cov.:

show subpopulations

Gnomad AFR

AF:

0.178

Gnomad AMI

AF:

0.199

Gnomad AMR

AF:

0.288

Gnomad ASJ

AF:

0.251

Gnomad EAS

AF:

0.120

Gnomad SAS

AF:

0.121

Gnomad FIN

AF:

0.246

Gnomad MID

AF:

0.297

Gnomad NFE

AF:

0.266

Gnomad OTH

AF:

0.253

GnomAD2 exomes

AF:

0.235

AC:

58512

AN:

249308

AF XY:

0.231

show subpopulations

Gnomad AFR exome

AF:

0.169

Gnomad AMR exome

AF:

0.304

Gnomad ASJ exome

AF:

0.244

Gnomad EAS exome

AF:

0.114

Gnomad FIN exome

AF:

0.254

Gnomad NFE exome

AF:

0.267

Gnomad OTH exome

AF:

0.266

GnomAD4 exome

AF:

0.257

AC:

374160

AN:

1455182

Hom.:

49910

Cov.:

AF XY:

0.253

AC XY:

183007

AN XY:

723982

show subpopulations

African (AFR)

AF:

0.169

AC:

5629

AN:

33332

American (AMR)

AF:

0.306

AC:

13571

AN:

44396

Ashkenazi Jewish (ASJ)

AF:

0.245

AC:

6368

AN:

25964

East Asian (EAS)

AF:

0.128

AC:

5078

AN:

39530

South Asian (SAS)

AF:

0.122

AC:

10452

AN:

85610

European-Finnish (FIN)

AF:

0.250

AC:

13323

AN:

53256

Middle Eastern (MID)

AF:

0.240

AC:

1376

AN:

5732

European-Non Finnish (NFE)

AF:

0.274

AC:

303777

AN:

1107382

Other (OTH)

AF:

0.243

AC:

14586

AN:

59980

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

14218

28436

42653

56871

71089

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.232

AC:

35376

AN:

152212

Hom.:

4358

Cov.:

AF XY:

0.231

AC XY:

17163

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.178

AC:

7403

AN:

41552

American (AMR)

AF:

0.289

AC:

4410

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.251

AC:

871

AN:

3472

East Asian (EAS)

AF:

0.121

AC:

623

AN:

5164

South Asian (SAS)

AF:

0.121

AC:

585

AN:

4828

European-Finnish (FIN)

AF:

0.246

AC:

2606

AN:

10606

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.266

AC:

18078

AN:

67992

Other (OTH)

AF:

0.253

AC:

533

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1419

2838

4258

5677

7096

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.256

Hom.:

15385

Bravo

AF:

0.237

Asia WGS

AF:

0.123

AC:

427

AN:

3478

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Mycobacterium tuberculosis, susceptibility to infection by

Other:1

Aug 23, 2005

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.27

CADD

Benign

(source)

DANN

Benign

0.87

PhyloP100

0.71

Mutation Taster

=291/9

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

Details are displayed if max score is > 0.2

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

Publications

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2-218384290-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over