Genetic Variant SLC11A1:n.-102_-101delGT (chr2-218381926-CGT-C) – ACMG Classification: Uncertain_significance (2 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The ENST00000468221.5(SLC11A1):n.-102_-101delGT variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00912 in 183,708 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 21)

Exomes 𝑓: 0.047 ( 0 hom. )

Consequence

SLC11A1
ENST00000468221.5 upstream_gene

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.180

Publications

14 publications found

Variant links:

COSMIC-nc: COSV51917355

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: Uncertain_significance. The variant received 2 ACMG points.

PM2

Variant has high frequency in the SAS (0.0522) population. However there is too low homozygotes in high coverage region: (expected more than 3, got 0).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000468221.5 link	n.-102_-101delGT		upstream_gene_variant		1
SLC11A1	ENST00000473367.5 link	n.-442_-441delGT		upstream_gene_variant		4		ENSP00000484905.1

Frequencies

GnomAD3 genomes

AF:

0.000209

AC:

AN:

148516

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000173

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000135

Gnomad ASJ

AF:

0.000292

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000424

Gnomad FIN

AF:

0.000304

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000239

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0469

AC:

1645

AN:

35106

Hom.:

AF XY:

0.0483

AC XY:

902

AN XY:

18690

show subpopulations

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

African (AFR)

AF:

0.0525

AC:

AN:

972

American (AMR)

AF:

0.0449

AC:

AN:

980

Ashkenazi Jewish (ASJ)

AF:

0.0488

AC:

AN:

1046

East Asian (EAS)

AF:

0.0470

AC:

118

AN:

2512

South Asian (SAS)

AF:

0.0596

AC:

164

AN:

2752

European-Finnish (FIN)

AF:

0.0427

AC:

141

AN:

3302

Middle Eastern (MID)

AF:

0.0368

AC:

AN:

136

European-Non Finnish (NFE)

AF:

0.0452

AC:

965

AN:

21348

Other (OTH)

AF:

0.0515

AC:

106

AN:

2058

⚠️ 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: 0.271

Heterozygous variant carriers

162

324

487

649

811

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000209

AC:

AN:

148602

Hom.:

Cov.:

AF XY:

0.000207

AC XY:

AN XY:

72348

show subpopulations

African (AFR)

AF:

0.000173

AC:

AN:

40470

American (AMR)

AF:

0.000134

AC:

AN:

14888

Ashkenazi Jewish (ASJ)

AF:

0.000292

AC:

AN:

3428

East Asian (EAS)

AF:

0.00

AC:

AN:

5064

South Asian (SAS)

AF:

0.000426

AC:

AN:

4694

European-Finnish (FIN)

AF:

0.000304

AC:

AN:

9856

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000239

AC:

AN:

66958

Other (OTH)

AF:

0.00

AC:

AN:

2054

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.431

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.18

Splicing

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

Publications

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2-218381926-CGTGTGTGT-CGTGTGT

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