Genetic Variant NM_000578.4:c.1389-85G>A (chr2-218394547-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_000578.4(SLC11A1):c.1389-85G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,462,860 control chromosomes in the GnomAD database, including 127,045 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 0.50 ( 22171 hom., cov: 33)

Exomes 𝑓: 0.39 ( 104874 hom. )

Consequence

SLC11A1
NM_000578.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.71

Publications

26 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=-0.83).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.821 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A1	NM_000578.4 link	c.1389-85G>A		intron_variant	Intron 13 of 14	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.1389-85G>A		intron_variant	Intron 13 of 14	1	NM_000578.4	ENSP00000233202.6		P49279-1

Frequencies

GnomAD3 genomes

AF:

0.498

AC:

75628

AN:

151974

Hom.:

22123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.828

Gnomad AMI

AF:

0.245

Gnomad AMR

AF:

0.431

Gnomad ASJ

AF:

0.348

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.313

Gnomad FIN

AF:

0.323

Gnomad MID

AF:

0.418

Gnomad NFE

AF:

0.379

Gnomad OTH

AF:

0.470

GnomAD4 exome

AF:

0.392

AC:

513182

AN:

1310768

Hom.:

104874

Cov.:

AF XY:

0.387

AC XY:

252017

AN XY:

651464

show subpopulations

African (AFR)

AF:

0.849

AC:

26312

AN:

30996

American (AMR)

AF:

0.422

AC:

17717

AN:

42026

Ashkenazi Jewish (ASJ)

AF:

0.355

AC:

8024

AN:

22610

East Asian (EAS)

AF:

0.305

AC:

11801

AN:

38716

South Asian (SAS)

AF:

0.314

AC:

24252

AN:

77202

European-Finnish (FIN)

AF:

0.326

AC:

12960

AN:

39712

Middle Eastern (MID)

AF:

0.368

AC:

1983

AN:

5382

European-Non Finnish (NFE)

AF:

0.388

AC:

387947

AN:

998944

Other (OTH)

AF:

0.402

AC:

22186

AN:

55180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

15276

30551

45827

61102

76378

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12226

24452

36678

48904

61130

<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:

0.498

AC:

75746

AN:

152092

Hom.:

22171

Cov.:

AF XY:

0.491

AC XY:

36528

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.828

AC:

34379

AN:

41508

American (AMR)

AF:

0.432

AC:

6597

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.348

AC:

1206

AN:

3468

East Asian (EAS)

AF:

0.296

AC:

1531

AN:

5166

South Asian (SAS)

AF:

0.312

AC:

1506

AN:

4826

European-Finnish (FIN)

AF:

0.323

AC:

3411

AN:

10568

Middle Eastern (MID)

AF:

0.418

AC:

123

AN:

294

European-Non Finnish (NFE)

AF:

0.379

AC:

25772

AN:

67956

Other (OTH)

AF:

0.472

AC:

998

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1640

3280

4919

6559

8199

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.424

Hom.:

5655

Bravo

AF:

0.522

Asia WGS

AF:

0.358

AC:

1247

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

0.25

(source)

DANN

Benign

0.44

PhyloP100

-2.7

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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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