2-189567551-C-G

Variant names:

• chr2-189567551-C-G
• rs4145237
• NM_014585.6:c.515-1952G>C

Variant summary

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

The NM_014585.6(SLC40A1):​c.515-1952G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.523 in 152,008 control chromosomes in the GnomAD database, including 23,502 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 0.52 (23502 hom., cov: 32)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.891
• Publications: 2 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: Labcorp Genetics (formerly Invitae), Genomics England PanelApp, PanelApp Australia, G2P, Orphanet, Ambry Genetics

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 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.515-1952G>C		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.515-1952G>C		intron	N/A	ENSP00000261024.3	Q9NP59
	SLC40A1	ENST00000852923.1		c.515-1952G>C		intron	N/A	ENSP00000522982.1
	SLC40A1	ENST00000852924.1		c.515-1952G>C		intron	N/A	ENSP00000522983.1

Frequencies

GnomAD3 genomes AF: 0.524 AC: 79533 AN: 151890 Hom.: 23511 Cov.: 32

Gnomad AFR AF: 0.228

Gnomad AMI AF: 0.805

Gnomad AMR AF: 0.666

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.786

Gnomad SAS AF: 0.634

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.621

Gnomad NFE AF: 0.621

Gnomad OTH AF: 0.575

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

GnomAD4 genome AF: 0.523 AC: 79511 AN: 152008 Hom.: 23502 Cov.: 32 AF XY: 0.528 AC XY: 39255 AN XY: 74324

African (AFR) AF: 0.228 AC: 9452 AN: 41484

American (AMR) AF: 0.666 AC: 10179 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2478 AN: 3472

East Asian (EAS) AF: 0.785 AC: 4062 AN: 5172

South Asian (SAS) AF: 0.633 AC: 3049 AN: 4818

European-Finnish (FIN) AF: 0.569 AC: 5993 AN: 10536

Middle Eastern (MID) AF: 0.606 AC: 177 AN: 292

European-Non Finnish (NFE) AF: 0.621 AC: 42179 AN: 67928

Other (OTH) AF: 0.573 AC: 1208 AN: 2108

Alfa AF: 0.556 Hom.: 3159

Bravo AF: 0.522

Asia WGS AF: 0.668 AC: 2320 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	11
DANN	Benign	0.66
PhyloP100		0.89
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: rs4145237; hg19: chr2-190432277; COSMIC: COSV107299732; COSMIC: COSV107299732;