Genetic Variant SLC11A1:n.-103_-102insGTGT (chr2-218381926-C-CGTGT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The ENST00000468221.5(SLC11A1):n.-103_-102insGTGT variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00433 in 185,388 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0041 ( 3 hom., cov: 21)

Exomes 𝑓: 0.0052 ( 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:

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000468221.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC11A1	ENST00000468221.5	TSL:1	n.-103_-102insGTGT		upstream_gene	N/A
	SLC11A1	ENST00000473367.5	TSL:4	n.-443_-442insGTGT		upstream_gene	N/A	ENSP00000484905.1

Frequencies

GnomAD3 genomes

AF:

0.00412

AC:

613

AN:

148766

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00450

Gnomad ASJ

AF:

0.00583

Gnomad EAS

AF:

0.000197

Gnomad SAS

AF:

0.00297

Gnomad FIN

AF:

0.000302

Gnomad MID

AF:

0.0194

Gnomad NFE

AF:

0.000954

Gnomad OTH

AF:

0.00491

GnomAD4 exome

AF:

0.00520

AC:

190

AN:

36532

Hom.:

AF XY:

0.00503

AC XY:

AN XY:

19480

show subpopulations

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

African (AFR)

AF:

0.0129

AC:

AN:

1010

American (AMR)

AF:

0.00201

AC:

AN:

994

Ashkenazi Jewish (ASJ)

AF:

0.00723

AC:

AN:

1106

East Asian (EAS)

AF:

0.00190

AC:

AN:

2628

South Asian (SAS)

AF:

0.00477

AC:

AN:

2932

European-Finnish (FIN)

AF:

0.00410

AC:

AN:

3418

Middle Eastern (MID)

AF:

0.0139

AC:

AN:

144

European-Non Finnish (NFE)

AF:

0.00546

AC:

121

AN:

22150

Other (OTH)

AF:

0.00512

AC:

AN:

2150

⚠️ 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: 0.307

Heterozygous variant carriers

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:

0.00411

AC:

612

AN:

148856

Hom.:

Cov.:

AF XY:

0.00393

AC XY:

285

AN XY:

72490

show subpopulations

African (AFR)

AF:

0.0105

AC:

427

AN:

40498

American (AMR)

AF:

0.00449

AC:

AN:

14910

Ashkenazi Jewish (ASJ)

AF:

0.00583

AC:

AN:

3428

East Asian (EAS)

AF:

0.000197

AC:

AN:

5064

South Asian (SAS)

AF:

0.00298

AC:

AN:

4698

European-Finnish (FIN)

AF:

0.000302

AC:

AN:

9938

Middle Eastern (MID)

AF:

0.0208

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.000954

AC:

AN:

67074

Other (OTH)

AF:

0.00486

AC:

AN:

2056

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

102

128

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.000150

Hom.:

139

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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-CGTGTGTGTGTGT

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over