rs4667287

Positions:

• chr2-189567149-C-A
• chr2-189567149-C-G
• chr2-189567149-C-T

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SLC40A1	NM_014585.6	c.515-1550G>T		intron_variant		ENST00000261024.7	NP_055400.1
SLC40A1	XM_047444066.1	c.395-1550G>T		intron_variant			XP_047300022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC40A1	ENST00000261024.7	c.515-1550G>T		intron_variant		1	NM_014585.6	ENSP00000261024	P1
SLC40A1	ENST00000427241.5	c.515-1550G>T		intron_variant		5		ENSP00000390005

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

Gnomad4 AFR AF: 0.737

Gnomad4 AMR AF: 0.872

Gnomad4 ASJ AF: 0.923

Gnomad4 EAS AF: 0.903

Gnomad4 SAS AF: 0.815

Gnomad4 FIN AF: 0.906

Gnomad4 NFE AF: 0.893

Gnomad4 OTH AF: 0.859

Alfa AF: 0.883 Hom.: 81921

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

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

Other links and lift over

dbSNP: rs4667287; hg19: chr2-190431875;