Variant 2-218395009-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000578.4(SLC11A1):c.1627G>A(p.Asp543Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0284 in 1,609,430 control chromosomes in the GnomAD database, including 1,304 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.041 ( 195 hom., cov: 33)

Exomes 𝑓: 0.027 ( 1109 hom. )

Consequence

SLC11A1
NM_000578.4 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -0.624

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014781058).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 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.1627G>A	p.Asp543Asn	missense_variant	15/15	ENST00000233202.11	NP_000569.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC11A1	ENST00000233202.11 linkuse as main transcript	c.1627G>A	p.Asp543Asn	missense_variant	15/15	1	NM_000578.4	ENSP00000233202	P1	P49279-1
SLC11A1	ENST00000468221.5 linkuse as main transcript	n.4754G>A		non_coding_transcript_exon_variant	13/13	1
SLC11A1	ENST00000354352.9 linkuse as main transcript	c.*1209G>A		3_prime_UTR_variant, NMD_transcript_variant	16/16	1		ENSP00000346320
SLC11A1	ENST00000465984.5 linkuse as main transcript	n.2103G>A		non_coding_transcript_exon_variant	13/14	2

Frequencies

GnomAD3 genomes

AF:

0.0412

AC:

6263

AN:

152186

Hom.:

197

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0632

Gnomad AMI

AF:

0.00987

Gnomad AMR

AF:

0.0638

Gnomad ASJ

AF:

0.0118

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.0639

Gnomad FIN

AF:

0.0225

Gnomad MID

AF:

0.0475

Gnomad NFE

AF:

0.0180

Gnomad OTH

AF:

0.0411

GnomAD3 exomes

AF:

0.0491

AC:

11852

AN:

241194

Hom.:

554

AF XY:

0.0454

AC XY:

5936

AN XY:

130718

show subpopulations

Gnomad AFR exome

AF:

0.0621

Gnomad AMR exome

AF:

0.114

Gnomad ASJ exome

AF:

0.0145

Gnomad EAS exome

AF:

0.139

Gnomad SAS exome

AF:

0.0544

Gnomad FIN exome

AF:

0.0216

Gnomad NFE exome

AF:

0.0197

Gnomad OTH exome

AF:

0.0337

GnomAD4 exome

AF:

0.0271

AC:

39430

AN:

1457126

Hom.:

1109

Cov.:

AF XY:

0.0273

AC XY:

19758

AN XY:

724476

show subpopulations

Gnomad4 AFR exome

AF:

0.0610

Gnomad4 AMR exome

AF:

0.104

Gnomad4 ASJ exome

AF:

0.0138

Gnomad4 EAS exome

AF:

0.118

Gnomad4 SAS exome

AF:

0.0531

Gnomad4 FIN exome

AF:

0.0198

Gnomad4 NFE exome

AF:

0.0179

Gnomad4 OTH exome

AF:

0.0354

GnomAD4 genome

AF:

0.0411

AC:

6266

AN:

152304

Hom.:

195

Cov.:

AF XY:

0.0428

AC XY:

3185

AN XY:

74470

show subpopulations

Gnomad4 AFR

AF:

0.0632

Gnomad4 AMR

AF:

0.0636

Gnomad4 ASJ

AF:

0.0118

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.0634

Gnomad4 FIN

AF:

0.0225

Gnomad4 NFE

AF:

0.0180

Gnomad4 OTH

AF:

0.0406

Alfa

AF:

0.0247

Hom.:

202

Bravo

AF:

0.0458

TwinsUK

AF:

0.0178

AC:

ALSPAC

AF:

0.0169

AC:

ESP6500AA

AF:

0.0611

AC:

269

ESP6500EA

AF:

0.0183

AC:

157

ExAC

AF:

0.0454

AC:

5507

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Buruli ulcer, susceptibility to

Other:1

risk factor, no assertion criteria provided

literature only

OMIM

Apr 01, 2006

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.0

DANN

Benign

0.96

DEOGEN2

Benign

0.23

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.50

MetaRNN

Benign

0.0015

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.6

MutationTaster

Benign

1.0

P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.49

REVEL

Benign

0.0050

Sift

Benign

0.057

Sift4G

Benign

0.097

Polyphen

0.078

Vest4

0.019

MPC

0.12

ClinPred

0.0029

GERP RS

-0.51

Varity_R

0.048

gMVP

0.14

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