Variant 2-218387907-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_000578.4(SLC11A1):c.747C>T(p.Gly249Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0598 in 1,607,688 control chromosomes in the GnomAD database, including 5,283 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.12 ( 1811 hom., cov: 32)

Exomes 𝑓: 0.054 ( 3472 hom. )

Consequence

SLC11A1
NM_000578.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -6.94

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:

SLC11A1 (HGNC:):

SLC11A1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 2-218387907-C-T is Benign according to our data. Variant chr2-218387907-C-T is described in ClinVar as [Benign]. Clinvar id is 3055354.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-6.94 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.281 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC11A1	NM_000578.4 linkuse as main transcript	c.747C>T	p.Gly249Gly	synonymous_variant	8/15	ENST00000233202.11	NP_000569.3	P49279-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000233202.11 linkuse as main transcript	c.747C>T	p.Gly249Gly	synonymous_variant	8/15	1	NM_000578.4	ENSP00000233202.6		P49279-1

Frequencies

GnomAD3 genomes

AF:

0.115

AC:

17530

AN:

151954

Hom.:

1808

Cov.:

show subpopulations

Gnomad AFR

AF:

0.285

Gnomad AMI

AF:

0.0384

Gnomad AMR

AF:

0.0683

Gnomad ASJ

AF:

0.0378

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.109

Gnomad FIN

AF:

0.0338

Gnomad MID

AF:

0.0673

Gnomad NFE

AF:

0.0424

Gnomad OTH

AF:

0.0912

GnomAD3 exomes

AF:

0.0702

AC:

16603

AN:

236632

Hom.:

1008

AF XY:

0.0667

AC XY:

8564

AN XY:

128334

show subpopulations

Gnomad AFR exome

AF:

0.286

Gnomad AMR exome

AF:

0.0675

Gnomad ASJ exome

AF:

0.0360

Gnomad EAS exome

AF:

0.106

Gnomad SAS exome

AF:

0.0942

Gnomad FIN exome

AF:

0.0297

Gnomad NFE exome

AF:

0.0401

Gnomad OTH exome

AF:

0.0537

GnomAD4 exome

AF:

0.0539

AC:

78519

AN:

1455616

Hom.:

3472

Cov.:

AF XY:

0.0544

AC XY:

39360

AN XY:

723672

show subpopulations

Gnomad4 AFR exome

AF:

0.294

Gnomad4 AMR exome

AF:

0.0644

Gnomad4 ASJ exome

AF:

0.0402

Gnomad4 EAS exome

AF:

0.0791

Gnomad4 SAS exome

AF:

0.0956

Gnomad4 FIN exome

AF:

0.0299

Gnomad4 NFE exome

AF:

0.0428

Gnomad4 OTH exome

AF:

0.0692

GnomAD4 genome

AF:

0.115

AC:

17560

AN:

152072

Hom.:

1811

Cov.:

AF XY:

0.115

AC XY:

8574

AN XY:

74368

show subpopulations

Gnomad4 AFR

AF:

0.285

Gnomad4 AMR

AF:

0.0681

Gnomad4 ASJ

AF:

0.0378

Gnomad4 EAS

AF:

0.109

Gnomad4 SAS

AF:

0.108

Gnomad4 FIN

AF:

0.0338

Gnomad4 NFE

AF:

0.0424

Gnomad4 OTH

AF:

0.0897

Alfa

AF:

0.0788

Hom.:

513

Bravo

AF:

0.125

Asia WGS

AF:

0.114

AC:

399

AN:

3478

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 22, 2024

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

-0.56

CADD

Benign

4.9

DANN

Benign

0.93

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

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