dbSNP rs1059823: SLC11A1:n.*1321A>G (chr2-218395121-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The ENST00000354352.9(SLC11A1):n.*1321A>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.427 in 1,035,212 control chromosomes in the GnomAD database, including 99,893 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 0.51 ( 22175 hom., cov: 32)

Exomes 𝑓: 0.41 ( 77718 hom. )

Consequence

SLC11A1
ENST00000354352.9 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.445

Publications

33 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=-0.9).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A1	NM_000578.4 link	c.*86A>G		3_prime_UTR_variant	Exon 15 of 15	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.*86A>G		3_prime_UTR_variant	Exon 15 of 15	1	NM_000578.4	ENSP00000233202.6		P49279-1

Frequencies

GnomAD3 genomes

AF:

0.508

AC:

77080

AN:

151834

Hom.:

22128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.799

Gnomad AMI

AF:

0.284

Gnomad AMR

AF:

0.455

Gnomad ASJ

AF:

0.365

Gnomad EAS

AF:

0.304

Gnomad SAS

AF:

0.330

Gnomad FIN

AF:

0.350

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.406

Gnomad OTH

AF:

0.486

GnomAD4 exome

AF:

0.413

AC:

364529

AN:

883260

Hom.:

77718

Cov.:

AF XY:

0.408

AC XY:

184091

AN XY:

451324

show subpopulations

African (AFR)

AF:

0.811

AC:

17915

AN:

22096

American (AMR)

AF:

0.451

AC:

15038

AN:

33354

Ashkenazi Jewish (ASJ)

AF:

0.376

AC:

7825

AN:

20814

East Asian (EAS)

AF:

0.313

AC:

10380

AN:

33210

South Asian (SAS)

AF:

0.331

AC:

22286

AN:

67254

European-Finnish (FIN)

AF:

0.353

AC:

12240

AN:

34692

Middle Eastern (MID)

AF:

0.385

AC:

1217

AN:

3164

European-Non Finnish (NFE)

AF:

0.415

AC:

260190

AN:

627712

Other (OTH)

AF:

0.426

AC:

17438

AN:

40964

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

11021

22043

33064

44086

55107

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6418

12836

19254

25672

32090

<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:

0.508

AC:

77202

AN:

151952

Hom.:

22175

Cov.:

AF XY:

0.502

AC XY:

37276

AN XY:

74270

show subpopulations

African (AFR)

AF:

0.799

AC:

33139

AN:

41464

American (AMR)

AF:

0.456

AC:

6957

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.365

AC:

1267

AN:

3470

East Asian (EAS)

AF:

0.305

AC:

1567

AN:

5136

South Asian (SAS)

AF:

0.329

AC:

1585

AN:

4814

European-Finnish (FIN)

AF:

0.350

AC:

3697

AN:

10568

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.406

AC:

27577

AN:

67932

Other (OTH)

AF:

0.488

AC:

1028

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1712

3424

5136

6848

8560

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

650

1300

1950

2600

3250

<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:

0.439

Hom.:

62426

Bravo

AF:

0.530

Asia WGS

AF:

0.365

AC:

1272

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

1.6

(source)

DANN

Benign

0.39

PhyloP100

0.45

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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