rs13404407

Variant names:

• chr2-189567244-T-C
• rs13404407
• NM_014585.6:c.515-1645A>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.515-1645A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0126 in 152,236 control chromosomes in the GnomAD database, including 18 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 0.013 (18 hom., cov: 32)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.712
• Publications: 4 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SLC40A1	NM_014585.6	c.515-1645A>G		intron_variant	Intron 5 of 7	ENST00000261024.7	NP_055400.1
SLC40A1	XM_047444066.1	c.395-1645A>G		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.515-1645A>G		intron_variant	Intron 5 of 7	1	NM_014585.6	ENSP00000261024.3
SLC40A1	ENST00000427241.5	c.515-1645A>G		intron_variant	Intron 7 of 7	5		ENSP00000390005.1

Frequencies

GnomAD3 genomes AF: 0.0126 AC: 1912 AN: 152116 Hom.: 17 Cov.: 32

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00805

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.0678

Gnomad SAS AF: 0.00933

Gnomad FIN AF: 0.000471

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00419

Gnomad OTH AF: 0.0120

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

GnomAD4 genome AF: 0.0126 AC: 1917 AN: 152236 Hom.: 18 Cov.: 32 AF XY: 0.0124 AC XY: 926 AN XY: 74450

African (AFR) AF: 0.0247 AC: 1025 AN: 41532

American (AMR) AF: 0.00804 AC: 123 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 44 AN: 3472

East Asian (EAS) AF: 0.0685 AC: 355 AN: 5180

South Asian (SAS) AF: 0.00954 AC: 46 AN: 4820

European-Finnish (FIN) AF: 0.000471 AC: 5 AN: 10606

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00419 AC: 285 AN: 68006

Other (OTH) AF: 0.0119 AC: 25 AN: 2108

Alfa AF: 0.00854 Hom.: 20

Bravo AF: 0.0142

Asia WGS AF: 0.0230 AC: 82 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.90
DANN	Benign	0.42
PhyloP100		-0.71
Mutation Taster		=100/0	polymorphism

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: rs13404407; hg19: chr2-190431970;