chr2-189567149-C-A

Variant names:

• chr2-189567149-C-A
• rs4667287
• NM_014585.6:c.515-1550G>T

Variant summary

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

The NM_014585.6(SLC40A1):​c.515-1550G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,128 control chromosomes in the GnomAD database, including 55,003 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 0.85 (55003 hom., cov: 31)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.381
• Publications: 10 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: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.887 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC40A1	NM_014585.6	c.515-1550G>T		intron_variant	Intron 5 of 7	ENST00000261024.7	NP_055400.1
SLC40A1	XM_047444066.1	c.395-1550G>T		intron_variant	Intron 5 of 7		XP_047300022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC40A1	ENST00000261024.7	c.515-1550G>T		intron_variant	Intron 5 of 7	1	NM_014585.6	ENSP00000261024.3
SLC40A1	ENST00000427241.5	c.515-1550G>T		intron_variant	Intron 7 of 7	5		ENSP00000390005.1

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128795 AN: 152010 Hom.: 54990 Cov.: 31

Gnomad AFR AF: 0.737

Gnomad AMI AF: 0.883

Gnomad AMR AF: 0.872

Gnomad ASJ AF: 0.923

Gnomad EAS AF: 0.903

Gnomad SAS AF: 0.816

Gnomad FIN AF: 0.906

Gnomad MID AF: 0.889

Gnomad NFE AF: 0.893

Gnomad OTH AF: 0.865

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

GnomAD4 genome AF: 0.847 AC: 128854 AN: 152128 Hom.: 55003 Cov.: 31 AF XY: 0.848 AC XY: 63074 AN XY: 74402

African (AFR) AF: 0.737 AC: 30535 AN: 41442

American (AMR) AF: 0.872 AC: 13324 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.923 AC: 3201 AN: 3468

East Asian (EAS) AF: 0.903 AC: 4669 AN: 5172

South Asian (SAS) AF: 0.815 AC: 3934 AN: 4828

European-Finnish (FIN) AF: 0.906 AC: 9608 AN: 10606

Middle Eastern (MID) AF: 0.888 AC: 261 AN: 294

European-Non Finnish (NFE) AF: 0.893 AC: 60702 AN: 68008

Other (OTH) AF: 0.859 AC: 1815 AN: 2112

Alfa AF: 0.879 Hom.: 102447

Bravo AF: 0.843

Asia WGS AF: 0.816 AC: 2842 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	4.6
DANN	Benign	0.72
PhyloP100		-0.38
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

Other links and lift over

dbSNP: rs4667287; hg19: chr2-190431875;