rs4145237

chr2-189567551-C-Gchr2-189567551-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.515-1952G>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

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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.765 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC40A1	NM_014585.6	c.515-1952G>C		intron_variant		ENST00000261024.7
SLC40A1	XM_047444066.1	c.395-1952G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC40A1	ENST00000261024.7	c.515-1952G>C		intron_variant		1	NM_014585.6	P1
SLC40A1	ENST00000427241.5	c.515-1952G>C		intron_variant		5

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

Gnomad4 AFR AF: 0.228

Gnomad4 AMR AF: 0.666

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.785

Gnomad4 SAS AF: 0.633

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.621

Gnomad4 OTH AF: 0.573

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
Cadd	Benign	11
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: rs4145237; hg19: chr2-190432277;