2-189567244-T-C

Position:

• chr2-189567244-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.515-1645A>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

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=-0.89).
• 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/exons	MANE	UniProt
SLC40A1	NM_014585.6	c.515-1645A>G		intron_variant		ENST00000261024.7
SLC40A1	XM_047444066.1	c.395-1645A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC40A1	ENST00000261024.7	c.515-1645A>G		intron_variant		1	NM_014585.6	P1
SLC40A1	ENST00000427241.5	c.515-1645A>G		intron_variant		5

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

Gnomad4 AFR AF: 0.0247

Gnomad4 AMR AF: 0.00804

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.0685

Gnomad4 SAS AF: 0.00954

Gnomad4 FIN AF: 0.000471

Gnomad4 NFE AF: 0.00419

Gnomad4 OTH AF: 0.0119

Alfa AF: 0.00675 Hom.: 10

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

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: rs13404407; hg19: chr2-190431970;