rs10202029

Positions:

• chr2-189581558-C-T

Variant summary

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

The ENST00000427419.5(SLC40A1):​c.-103+344G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0864 in 152,396 control chromosomes in the GnomAD database, including 1,119 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 0.086 (1118 hom., cov: 31)
  • Exomes 𝑓: 0.032 (1 hom.)
• Consequence: SLC40A1 ENST00000427419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800

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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC40A1	ENST00000427419.5	c.-103+344G>A		intron_variant		1		ENSP00000392730
SLC40A1	ENST00000440626.1	c.-64-1034G>A		intron_variant		1		ENSP00000396134
SLC40A1	ENST00000427241.5	c.-102-996G>A		intron_variant		5		ENSP00000390005
SLC40A1	ENST00000455320.5	c.-103+150G>A		intron_variant		3		ENSP00000413549

Frequencies

GnomAD3 genomes AF: 0.0863 AC: 13119 AN: 152026 Hom.: 1116 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.0838

Gnomad FIN AF: 0.0188

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0831

GnomAD4 exome AF: 0.0317 AC: 8 AN: 252 Hom.: 1 AF XY: 0.0357 AC XY: 7 AN XY: 196

Gnomad4 AFR exome AF: 0.500

Gnomad4 AMR exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0324

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0864 AC: 13152 AN: 152144 Hom.: 1118 Cov.: 31 AF XY: 0.0850 AC XY: 6325 AN XY: 74384

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0521

Gnomad4 ASJ AF: 0.0404

Gnomad4 EAS AF: 0.0247

Gnomad4 SAS AF: 0.0845

Gnomad4 FIN AF: 0.0188

Gnomad4 NFE AF: 0.0326

Gnomad4 OTH AF: 0.0818

Alfa AF: 0.0544 Hom.: 115

Bravo AF: 0.0953

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs10202029; hg19: chr2-190446284;