2-189567887-T-C

Position:

• chr2-189567887-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014585.6(SLC40A1):​c.515-2288A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0844 in 152,240 control chromosomes in the GnomAD database, including 1,342 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 0.084 (1342 hom., cov: 32)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.264

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.239 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC40A1	NM_014585.6	c.515-2288A>G		intron_variant		ENST00000261024.7
SLC40A1	XM_047444066.1	c.395-2288A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC40A1	ENST00000261024.7	c.515-2288A>G		intron_variant		1	NM_014585.6	P1
SLC40A1	ENST00000427241.5	c.515-2288A>G		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0842 AC: 12812 AN: 152122 Hom.: 1339 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.0418

Gnomad AMR AF: 0.0523

Gnomad ASJ AF: 0.0749

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0251

Gnomad FIN AF: 0.0142

Gnomad MID AF: 0.0732

Gnomad NFE AF: 0.0179

Gnomad OTH AF: 0.0823

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

GnomAD4 genome AF: 0.0844 AC: 12848 AN: 152240 Hom.: 1342 Cov.: 32 AF XY: 0.0818 AC XY: 6090 AN XY: 74448

Gnomad4 AFR AF: 0.243

Gnomad4 AMR AF: 0.0522

Gnomad4 ASJ AF: 0.0749

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0247

Gnomad4 FIN AF: 0.0142

Gnomad4 NFE AF: 0.0179

Gnomad4 OTH AF: 0.0810

Alfa AF: 0.0616 Hom.: 132

Bravo AF: 0.0966

Asia WGS AF: 0.0240 AC: 84 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	4.7
DANN	Benign	0.66

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: rs10188230; hg19: chr2-190432613;