rs1123109

chr2-189579666-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.111+147A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 742,714 control chromosomes in the GnomAD database, including 14,902 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 0.16 (2424 hom., cov: 33)
  • Exomes 𝑓: 0.19 (12478 hom.)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0700

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC40A1	NM_014585.6	c.111+147A>G		intron_variant		ENST00000261024.7
SLC40A1	XM_047444066.1	c.-145+147A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC40A1	ENST00000261024.7	c.111+147A>G		intron_variant		1	NM_014585.6	P1

Frequencies

GnomAD3 genomes AF: 0.157 AC: 23823 AN: 152128 Hom.: 2423 Cov.: 33

Gnomad AFR AF: 0.0469

Gnomad AMI AF: 0.0954

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.129

Gnomad EAS AF: 0.0494

Gnomad SAS AF: 0.149

Gnomad FIN AF: 0.243

Gnomad MID AF: 0.174

Gnomad NFE AF: 0.230

Gnomad OTH AF: 0.152

GnomAD4 exome AF: 0.195 AC: 114889 AN: 590468 Hom.: 12478 AF XY: 0.195 AC XY: 61822 AN XY: 317518

Gnomad4 AFR exome AF: 0.0447

Gnomad4 AMR exome AF: 0.0896

Gnomad4 ASJ exome AF: 0.131

Gnomad4 EAS exome AF: 0.0472

Gnomad4 SAS exome AF: 0.152

Gnomad4 FIN exome AF: 0.235

Gnomad4 NFE exome AF: 0.233

Gnomad4 OTH exome AF: 0.182

GnomAD4 genome AF: 0.156 AC: 23823 AN: 152246 Hom.: 2424 Cov.: 33 AF XY: 0.154 AC XY: 11486 AN XY: 74418

Gnomad4 AFR AF: 0.0468

Gnomad4 AMR AF: 0.118

Gnomad4 ASJ AF: 0.129

Gnomad4 EAS AF: 0.0492

Gnomad4 SAS AF: 0.149

Gnomad4 FIN AF: 0.243

Gnomad4 NFE AF: 0.230

Gnomad4 OTH AF: 0.151

Alfa AF: 0.204 Hom.: 4506

Bravo AF: 0.140

Asia WGS AF: 0.102 AC: 356 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	2.2
Dann	Benign	0.26

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: rs1123109; hg19: chr2-190444392;