Genetic Variant NM_000578.4:c.572-80C>T (chr2-218387485-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 NM_000578.4(SLC11A1):c.572-80C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0638 in 1,426,706 control chromosomes in the GnomAD database, including 3,367 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 0.081 ( 576 hom., cov: 33)

Exomes 𝑓: 0.062 ( 2791 hom. )

Consequence

SLC11A1
NM_000578.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0480

Publications

15 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 = 0.132 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A1	NM_000578.4 link	c.572-80C>T		intron_variant	Intron 6 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.572-80C>T		intron_variant	Intron 6 of 14	1	NM_000578.4	ENSP00000233202.6		P49279-1

Frequencies

GnomAD3 genomes

AF:

0.0806

AC:

12261

AN:

152158

Hom.:

576

Cov.:

show subpopulations

Gnomad AFR

AF:

0.135

Gnomad AMI

AF:

0.0385

Gnomad AMR

AF:

0.0584

Gnomad ASJ

AF:

0.0550

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.114

Gnomad FIN

AF:

0.0409

Gnomad MID

AF:

0.0701

Gnomad NFE

AF:

0.0560

Gnomad OTH

AF:

0.0742

GnomAD4 exome

AF:

0.0618

AC:

78785

AN:

1274430

Hom.:

2791

AF XY:

0.0632

AC XY:

40579

AN XY:

642574

show subpopulations

African (AFR)

AF:

0.133

AC:

3883

AN:

29160

American (AMR)

AF:

0.0632

AC:

2649

AN:

41916

Ashkenazi Jewish (ASJ)

AF:

0.0554

AC:

1330

AN:

23998

East Asian (EAS)

AF:

0.0794

AC:

3087

AN:

38896

South Asian (SAS)

AF:

0.103

AC:

8231

AN:

80202

European-Finnish (FIN)

AF:

0.0345

AC:

1828

AN:

52946

Middle Eastern (MID)

AF:

0.0820

AC:

441

AN:

5378

European-Non Finnish (NFE)

AF:

0.0565

AC:

53596

AN:

947984

Other (OTH)

AF:

0.0693

AC:

3740

AN:

53950

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

3999

7998

11997

15996

19995

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1988

3976

5964

7952

9940

<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:

0.0806

AC:

12276

AN:

152276

Hom.:

576

Cov.:

AF XY:

0.0810

AC XY:

6031

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.135

AC:

5617

AN:

41560

American (AMR)

AF:

0.0582

AC:

891

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0550

AC:

191

AN:

3470

East Asian (EAS)

AF:

0.111

AC:

575

AN:

5186

South Asian (SAS)

AF:

0.114

AC:

550

AN:

4816

European-Finnish (FIN)

AF:

0.0409

AC:

434

AN:

10604

Middle Eastern (MID)

AF:

0.0685

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0560

AC:

3808

AN:

68024

Other (OTH)

AF:

0.0734

AC:

155

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

590

1180

1770

2360

2950

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<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:

0.0609

Hom.:

975

Bravo

AF:

0.0843

Asia WGS

AF:

0.102

AC:

357

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

4.7

(source)

DANN

Benign

0.63

PhyloP100

0.048

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