dbSNP rs3816560: SLC11A1:c.954+91T>C (chr2-218390119-T-C) – 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.954+91T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.263 in 1,341,436 control chromosomes in the GnomAD database, including 48,279 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 0.25 ( 4979 hom., cov: 31)

Exomes 𝑓: 0.26 ( 43300 hom. )

Consequence

SLC11A1
NM_000578.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.498

Publications

23 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=-0.88).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC11A1	NM_000578.4 link	c.954+91T>C		intron_variant	Intron 9 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.954+91T>C		intron_variant	Intron 9 of 14	1	NM_000578.4	ENSP00000233202.6		P49279-1

Frequencies

GnomAD3 genomes

AF:

0.251

AC:

38164

AN:

151908

Hom.:

4975

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.313

Gnomad AMR

AF:

0.300

Gnomad ASJ

AF:

0.261

Gnomad EAS

AF:

0.127

Gnomad SAS

AF:

0.136

Gnomad FIN

AF:

0.257

Gnomad MID

AF:

0.332

Gnomad NFE

AF:

0.272

Gnomad OTH

AF:

0.272

GnomAD4 exome

AF:

0.265

AC:

314956

AN:

1189410

Hom.:

43300

AF XY:

0.261

AC XY:

153799

AN XY:

589572

show subpopulations

African (AFR)

AF:

0.226

AC:

6016

AN:

26660

American (AMR)

AF:

0.308

AC:

7940

AN:

25752

Ashkenazi Jewish (ASJ)

AF:

0.258

AC:

4803

AN:

18650

East Asian (EAS)

AF:

0.135

AC:

5052

AN:

37502

South Asian (SAS)

AF:

0.136

AC:

8875

AN:

65374

European-Finnish (FIN)

AF:

0.260

AC:

12601

AN:

48454

Middle Eastern (MID)

AF:

0.269

AC:

1062

AN:

3952

European-Non Finnish (NFE)

AF:

0.280

AC:

255830

AN:

912944

Other (OTH)

AF:

0.255

AC:

12777

AN:

50122

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

10988

21976

32964

43952

54940

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8318

16636

24954

33272

41590

<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:

0.251

AC:

38191

AN:

152026

Hom.:

4979

Cov.:

AF XY:

0.249

AC XY:

18470

AN XY:

74298

show subpopulations

African (AFR)

AF:

0.222

AC:

9208

AN:

41468

American (AMR)

AF:

0.301

AC:

4588

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.261

AC:

903

AN:

3464

East Asian (EAS)

AF:

0.127

AC:

657

AN:

5170

South Asian (SAS)

AF:

0.136

AC:

657

AN:

4816

European-Finnish (FIN)

AF:

0.257

AC:

2718

AN:

10560

Middle Eastern (MID)

AF:

0.330

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.272

AC:

18499

AN:

67966

Other (OTH)

AF:

0.274

AC:

579

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1446

2892

4337

5783

7229

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

396

792

1188

1584

1980

<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:

0.261

Hom.:

3187

Bravo

AF:

0.257

Asia WGS

AF:

0.148

AC:

514

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

6.5

(source)

DANN

Benign

0.49

PhyloP100

-0.50

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