dbSNP rs7573065: SLC11A1:n.-45C>A (chr2-218381984-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000468221.5(SLC11A1):n.-45C>A variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000708 in 282,392 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0000076 ( 0 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: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	Protein	UniProt
SLC11A1	ENST00000468221.5 link	n.-45C>A	upstream_gene_variant	1
SLC11A1	ENST00000539932.5 link	n.-385C>A	upstream_gene_variant	1	ENSP00000443435.2	A0A0A0MTL3
SLC11A1	ENST00000465984.5 link	n.-204C>A	upstream_gene_variant	2

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151012

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000661

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000761

AC:

AN:

131380

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

68862

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

3820

American (AMR)

AF:

0.000237

AC:

AN:

4214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

4248

East Asian (EAS)

AF:

0.00

AC:

AN:

8752

South Asian (SAS)

AF:

0.00

AC:

AN:

11520

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10756

Middle Eastern (MID)

AF:

0.00

AC:

AN:

596

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

79674

Other (OTH)

AF:

0.00

AC:

AN:

7800

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.275

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00000662

AC:

AN:

151012

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73582

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

40970

American (AMR)

AF:

0.0000661

AC:

AN:

15128

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3462

East Asian (EAS)

AF:

0.00

AC:

AN:

5168

South Asian (SAS)

AF:

0.00

AC:

AN:

4794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10358

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67834

Other (OTH)

AF:

0.00

AC:

AN:

2078

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.625

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

422

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

6.8

(source)

DANN

Benign

0.40

PhyloP100

0.077

PromoterAI

-0.090

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over