rs930373

Positions:

• chr2-189578857-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+956A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.923 in 152,246 control chromosomes in the GnomAD database, including 64,958 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 0.92 (64958 hom., cov: 31)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.327

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=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC40A1	NM_014585.6	c.111+956A>G		intron_variant		ENST00000261024.7	NP_055400.1
SLC40A1	XM_047444066.1	c.-144-504A>G		intron_variant			XP_047300022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC40A1	ENST00000261024.7	c.111+956A>G		intron_variant		1	NM_014585.6	ENSP00000261024	P1

Frequencies

GnomAD3 genomes AF: 0.923 AC: 140424 AN: 152128 Hom.: 64907 Cov.: 31

Gnomad AFR AF: 0.877

Gnomad AMI AF: 0.790

Gnomad AMR AF: 0.935

Gnomad ASJ AF: 0.940

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.960

Gnomad MID AF: 0.934

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.928

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

GnomAD4 genome AF: 0.923 AC: 140533 AN: 152246 Hom.: 64958 Cov.: 31 AF XY: 0.926 AC XY: 68907 AN XY: 74448

Gnomad4 AFR AF: 0.877

Gnomad4 AMR AF: 0.935

Gnomad4 ASJ AF: 0.940

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.981

Gnomad4 FIN AF: 0.960

Gnomad4 NFE AF: 0.934

Gnomad4 OTH AF: 0.929

Alfa AF: 0.929 Hom.: 24364

Bravo AF: 0.919

Asia WGS AF: 0.985 AC: 3421 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	4.7
DANN	Benign	0.43

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: rs930373; hg19: chr2-190443583;