Variant chr2-218383067-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6BP7BA1

The NM_000578.4(SLC11A1):c.115C>T(p.Leu39=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0101 in 1,613,940 control chromosomes in the GnomAD database, including 932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.043 ( 479 hom., cov: 31)

Exomes 𝑓: 0.0066 ( 453 hom. )

Consequence

SLC11A1
NM_000578.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.133

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.42).

BP6

Variant 2-218383067-C-T is Benign according to our data. Variant chr2-218383067-C-T is described in ClinVar as [Benign]. Clinvar id is 3055747.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=0.133 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.139 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC11A1	NM_000578.4 linkuse as main transcript	c.115C>T	p.Leu39=	synonymous_variant	2/15	ENST00000233202.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC11A1	ENST00000233202.11 linkuse as main transcript	c.115C>T	p.Leu39=	synonymous_variant	2/15	1	NM_000578.4	P1	P49279-1

Frequencies

GnomAD3 genomes

AF:

0.0431

AC:

6554

AN:

152072

Hom.:

479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.141

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0227

Gnomad ASJ

AF:

0.0161

Gnomad EAS

AF:

0.00483

Gnomad SAS

AF:

0.0178

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.00150

Gnomad OTH

AF:

0.0349

GnomAD3 exomes

AF:

0.0152

AC:

3771

AN:

248498

Hom.:

180

AF XY:

0.0122

AC XY:

1637

AN XY:

134568

show subpopulations

Gnomad AFR exome

AF:

0.149

Gnomad AMR exome

AF:

0.0110

Gnomad ASJ exome

AF:

0.0154

Gnomad EAS exome

AF:

0.00577

Gnomad SAS exome

AF:

0.0164

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00131

Gnomad OTH exome

AF:

0.0119

GnomAD4 exome

AF:

0.00662

AC:

9674

AN:

1461750

Hom.:

453

Cov.:

AF XY:

0.00636

AC XY:

4625

AN XY:

727164

show subpopulations

Gnomad4 AFR exome

AF:

0.154

Gnomad4 AMR exome

AF:

0.0119

Gnomad4 ASJ exome

AF:

0.0160

Gnomad4 EAS exome

AF:

0.00539

Gnomad4 SAS exome

AF:

0.0152

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000934

Gnomad4 OTH exome

AF:

0.0146

GnomAD4 genome

AF:

0.0432

AC:

6581

AN:

152190

Hom.:

479

Cov.:

AF XY:

0.0416

AC XY:

3093

AN XY:

74426

show subpopulations

Gnomad4 AFR

AF:

0.142

Gnomad4 AMR

AF:

0.0226

Gnomad4 ASJ

AF:

0.0161

Gnomad4 EAS

AF:

0.00484

Gnomad4 SAS

AF:

0.0178

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00150

Gnomad4 OTH

AF:

0.0369

Alfa

AF:

0.0196

Hom.:

131

Bravo

AF:

0.0478

Asia WGS

AF:

0.0340

AC:

118

AN:

3478

EpiCase

AF:

0.00191

EpiControl

AF:

0.00237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SLC11A1-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jan 28, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.42

CADD

Benign

9.0

DANN

Benign

0.73

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over