chr2-189576921-T-A

Position:

• chr2-189576921-T-A

Variant summary

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

The NM_014585.6(SLC40A1):​c.112-1601A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0703 in 152,306 control chromosomes in the GnomAD database, including 1,067 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 0.070 (1067 hom., cov: 32)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0680

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]

SLC40A1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC40A1	NM_014585.6	c.112-1601A>T		intron_variant		ENST00000261024.7	NP_055400.1
SLC40A1	XM_047444066.1	c.-10+1298A>T		intron_variant			XP_047300022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC40A1	ENST00000261024.7	c.112-1601A>T		intron_variant		1	NM_014585.6	ENSP00000261024.3

Frequencies

GnomAD3 genomes AF: 0.0700 AC: 10658 AN: 152188 Hom.: 1054 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0291

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0977

Gnomad SAS AF: 0.0159

Gnomad FIN AF: 0.000565

Gnomad MID AF: 0.0475

Gnomad NFE AF: 0.00545

Gnomad OTH AF: 0.0659

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0703 AC: 10710 AN: 152306 Hom.: 1067 Cov.: 32 AF XY: 0.0687 AC XY: 5115 AN XY: 74478

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.0290

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.0981

Gnomad4 SAS AF: 0.0161

Gnomad4 FIN AF: 0.000565

Gnomad4 NFE AF: 0.00545

Gnomad4 OTH AF: 0.0647

Alfa AF: 0.0408 Hom.: 74

Bravo AF: 0.0817

Asia WGS AF: 0.0460 AC: 161 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.1
DANN	Benign	0.61

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: rs3792079; hg19: chr2-190441647;