Variant 2-189580558-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBA1

The NM_014585.6(SLC40A1):c.-98G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 1,601,060 control chromosomes in the GnomAD database, including 35,289 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.16 ( 2425 hom., cov: 33)

Exomes 𝑓: 0.21 ( 32864 hom. )

Consequence

SLC40A1
NM_014585.6 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.62

Variant links:

Genes affected

SLC40A1 (HGNC:10909): (solute carrier family 40 member 1) The protein encoded by this gene is a cell membrane protein that may be involved in iron export from duodenal epithelial cells. Defects in this gene are a cause of hemochromatosis type 4 (HFE4). [provided by RefSeq, Jul 2008]

SLC40A1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.25).

BP6

Variant 2-189580558-C-G is Benign according to our data. Variant chr2-189580558-C-G is described in ClinVar as [Benign]. Clinvar id is 260421.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC40A1	NM_014585.6 linkuse as main transcript	c.-98G>C		5_prime_UTR_variant	1/8	ENST00000261024.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC40A1	ENST00000261024.7 linkuse as main transcript	c.-98G>C		5_prime_UTR_variant	1/8	1	NM_014585.6	P1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

23809

AN:

152086

Hom.:

2424

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0467

Gnomad AMI

AF:

0.0956

Gnomad AMR

AF:

0.118

Gnomad ASJ

AF:

0.127

Gnomad EAS

AF:

0.0492

Gnomad SAS

AF:

0.147

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.175

Gnomad NFE

AF:

0.230

Gnomad OTH

AF:

0.151

GnomAD3 exomes

AF:

0.166

AC:

38940

AN:

235258

Hom.:

3808

AF XY:

0.172

AC XY:

21978

AN XY:

127772

show subpopulations

Gnomad AFR exome

AF:

0.0408

Gnomad AMR exome

AF:

0.0812

Gnomad ASJ exome

AF:

0.123

Gnomad EAS exome

AF:

0.0448

Gnomad SAS exome

AF:

0.148

Gnomad FIN exome

AF:

0.239

Gnomad NFE exome

AF:

0.228

Gnomad OTH exome

AF:

0.172

GnomAD4 exome

AF:

0.206

AC:

298890

AN:

1448854

Hom.:

32864

Cov.:

AF XY:

0.206

AC XY:

148279

AN XY:

720772

show subpopulations

Gnomad4 AFR exome

AF:

0.0393

Gnomad4 AMR exome

AF:

0.0860

Gnomad4 ASJ exome

AF:

0.126

Gnomad4 EAS exome

AF:

0.0475

Gnomad4 SAS exome

AF:

0.150

Gnomad4 FIN exome

AF:

0.238

Gnomad4 NFE exome

AF:

0.228

Gnomad4 OTH exome

AF:

0.184

GnomAD4 genome

AF:

0.156

AC:

23809

AN:

152206

Hom.:

2425

Cov.:

AF XY:

0.154

AC XY:

11485

AN XY:

74408

show subpopulations

Gnomad4 AFR

AF:

0.0466

Gnomad4 AMR

AF:

0.118

Gnomad4 ASJ

AF:

0.127

Gnomad4 EAS

AF:

0.0489

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.243

Gnomad4 NFE

AF:

0.230

Gnomad4 OTH

AF:

0.150

Alfa

AF:

0.190

Hom.:

560

Bravo

AF:

0.140

Asia WGS

AF:

0.102

AC:

356

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Hemochromatosis type 4

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.91

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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