2-189568563-C-T

Variant names:

• chr2-189568563-C-T
• rs16831659
• NM_014585.6:c.515-2964G>A

Variant summary

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

The NM_014585.6(SLC40A1):​c.515-2964G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0787 in 152,146 control chromosomes in the GnomAD database, including 654 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 0.079 (654 hom., cov: 33)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.515
• 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: 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=-0.94).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.169 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.515-2964G>A		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.515-2964G>A		intron	N/A	ENSP00000261024.3	Q9NP59
	SLC40A1	ENST00000852923.1		c.515-2964G>A		intron	N/A	ENSP00000522982.1
	SLC40A1	ENST00000852924.1		c.515-2964G>A		intron	N/A	ENSP00000522983.1

Frequencies

GnomAD3 genomes AF: 0.0786 AC: 11950 AN: 152034 Hom.: 648 Cov.: 33

Gnomad AFR AF: 0.0296

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.0744

Gnomad EAS AF: 0.0196

Gnomad SAS AF: 0.177

Gnomad FIN AF: 0.0947

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0812

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

GnomAD4 genome AF: 0.0787 AC: 11967 AN: 152146 Hom.: 654 Cov.: 33 AF XY: 0.0794 AC XY: 5902 AN XY: 74362

African (AFR) AF: 0.0296 AC: 1228 AN: 41522

American (AMR) AF: 0.0630 AC: 963 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0744 AC: 258 AN: 3470

East Asian (EAS) AF: 0.0195 AC: 101 AN: 5182

South Asian (SAS) AF: 0.178 AC: 860 AN: 4818

European-Finnish (FIN) AF: 0.0947 AC: 1000 AN: 10556

Middle Eastern (MID) AF: 0.102 AC: 30 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7235 AN: 67990

Other (OTH) AF: 0.0874 AC: 185 AN: 2116

Alfa AF: 0.0939 Hom.: 902

Bravo AF: 0.0698

Asia WGS AF: 0.129 AC: 446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.70
DANN	Benign	0.54
PhyloP100		-0.52
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: rs16831659;

hg19: chr2-190433289;