chr2-189567887-T-C

Variant names:

• chr2-189567887-T-C
• rs10188230
• NM_014585.6:c.515-2288A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014585.6(SLC40A1):​c.515-2288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,240 control chromosomes in the GnomAD database, including 1,342 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 0.084 (1342 hom., cov: 32)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• hemochromatosis type 4

  Inheritance: AD, AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Ambry Genetics, PanelApp Australia, Genomics England PanelApp, G2P, Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014585.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC40A1	NM_014585.6	MANE Select	c.515-2288A>G		intron	N/A	NP_055400.1	Q9NP59

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC40A1	ENST00000261024.7	TSL:1 MANE Select	c.515-2288A>G		intron	N/A	ENSP00000261024.3	Q9NP59
	SLC40A1	ENST00000852923.1		c.515-2288A>G		intron	N/A	ENSP00000522982.1
	SLC40A1	ENST00000852924.1		c.515-2288A>G		intron	N/A	ENSP00000522983.1

Frequencies

GnomAD3 genomes AF: 0.0842 AC: 12812 AN: 152122 Hom.: 1339 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0823

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0844 AC: 12848 AN: 152240 Hom.: 1342 Cov.: 32 AF XY: 0.0818 AC XY: 6090 AN XY: 74448

African (AFR) AF: 0.243 AC: 10069 AN: 41486

American (AMR) AF: 0.0522 AC: 799 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.0749 AC: 260 AN: 3470

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5192

South Asian (SAS) AF: 0.0247 AC: 119 AN: 4826

European-Finnish (FIN) AF: 0.0142 AC: 151 AN: 10622

Middle Eastern (MID) AF: 0.0788 AC: 23 AN: 292

European-Non Finnish (NFE) AF: 0.0179 AC: 1215 AN: 68026

Other (OTH) AF: 0.0810 AC: 171 AN: 2112

Alfa AF: 0.0680 Hom.: 164

Bravo AF: 0.0966

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.66
PhyloP100		0.26
Mutation Taster		=100/0	polymorphism (auto)

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs10188230;

hg19: chr2-190432613;