rs7596205

chr2-189563467-G-Achr2-189563467-G-T

Variant summary

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

The NM_014585.6(SLC40A1):c.1402+117C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0962 in 842,504 control chromosomes in the GnomAD database, including 4,494 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 0.078 (651 hom., cov: 32)
  • Exomes 𝑓: 0.10 (3843 hom.)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.690

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 (SAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SLC40A1	NM_014585.6	c.1402+117C>T		intron_variant		ENST00000261024.7
SLC40A1	XM_047444066.1	c.1282+117C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SLC40A1	ENST00000261024.7	c.1402+117C>T		intron_variant		1	NM_014585.6	P1

Frequencies

GnomAD3 genomes AF: 0.0784 AC: 11913 AN: 151948 Hom.: 645 Cov.: 32

Gnomad AFR AF: 0.0294

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.0631

Gnomad ASJ AF: 0.0743

Gnomad EAS AF: 0.0190

Gnomad SAS AF: 0.176

Gnomad FIN AF: 0.0941

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0810

GnomAD4 exome AF: 0.100 AC: 69124 AN: 690442 Hom.: 3843 AF XY: 0.102 AC XY: 35956 AN XY: 351280

Gnomad4 AFR exome AF: 0.0262

Gnomad4 AMR exome AF: 0.0548

Gnomad4 ASJ exome AF: 0.0712

Gnomad4 EAS exome AF: 0.0259

Gnomad4 SAS exome AF: 0.168

Gnomad4 FIN exome AF: 0.0949

Gnomad4 NFE exome AF: 0.105

Gnomad4 OTH exome AF: 0.0930

GnomAD4 genome AF: 0.0785 AC: 11930 AN: 152062 Hom.: 651 Cov.: 32 AF XY: 0.0791 AC XY: 5877 AN XY: 74344

Gnomad4 AFR AF: 0.0294

Gnomad4 AMR AF: 0.0630

Gnomad4 ASJ AF: 0.0743

Gnomad4 EAS AF: 0.0189

Gnomad4 SAS AF: 0.178

Gnomad4 FIN AF: 0.0941

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0873

Alfa AF: 0.0977 Hom.: 782

Bravo AF: 0.0698

Asia WGS AF: 0.127 AC: 440 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	0.27
Dann	Benign	0.50

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: rs7596205; hg19: chr2-190428193;