2-189579473-G-A

Variant names:

• chr2-189579473-G-A
• rs1123110
• NM_014585.6:c.111+340C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014585.6(SLC40A1):​c.111+340C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.559 in 151,994 control chromosomes in the GnomAD database, including 25,269 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 0.56 (25269 hom., cov: 32)
• Consequence: SLC40A1 NM_014585.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.03
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• hemochromatosis type 4

  Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_014585.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC40A1	NM_014585.6	MANE Select	c.111+340C>T		intron	N/A	NP_055400.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SLC40A1	ENST00000261024.7	TSL:1 MANE Select	c.111+340C>T		intron	N/A	ENSP00000261024.3
	SLC40A1	ENST00000479598.5	TSL:1	n.392+340C>T		intron	N/A
	SLC40A1	ENST00000852923.1		c.111+340C>T		intron	N/A	ENSP00000522982.1

Frequencies

GnomAD3 genomes AF: 0.560 AC: 84988 AN: 151874 Hom.: 25263 Cov.: 32

Gnomad AFR AF: 0.349

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.647

Gnomad ASJ AF: 0.690

Gnomad EAS AF: 0.810

Gnomad SAS AF: 0.600

Gnomad FIN AF: 0.657

Gnomad MID AF: 0.545

Gnomad NFE AF: 0.624

Gnomad OTH AF: 0.573

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

GnomAD4 genome AF: 0.559 AC: 85023 AN: 151994 Hom.: 25269 Cov.: 32 AF XY: 0.565 AC XY: 41952 AN XY: 74294

African (AFR) AF: 0.348 AC: 14424 AN: 41404

American (AMR) AF: 0.647 AC: 9888 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.690 AC: 2395 AN: 3472

East Asian (EAS) AF: 0.810 AC: 4196 AN: 5180

South Asian (SAS) AF: 0.600 AC: 2894 AN: 4820

European-Finnish (FIN) AF: 0.657 AC: 6939 AN: 10562

Middle Eastern (MID) AF: 0.545 AC: 159 AN: 292

European-Non Finnish (NFE) AF: 0.624 AC: 42425 AN: 67950

Other (OTH) AF: 0.571 AC: 1207 AN: 2114

Alfa AF: 0.607 Hom.: 108589

Bravo AF: 0.554

Asia WGS AF: 0.646 AC: 2243 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.68
DANN	Benign	0.51
PhyloP100		-1.0
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1123110; hg19: chr2-190444199;