rs10202029

Variant names:

• chr2-189581558-C-T
• rs10202029
• ENST00000427419.5:c.-103+344G>A

Variant summary

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

The ENST00000427419.5(SLC40A1):​c.-103+344G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0864 in 152,396 control chromosomes in the GnomAD database, including 1,119 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 0.086 (1118 hom., cov: 31)
  • Exomes 𝑓: 0.032 (1 hom.)
• Consequence: SLC40A1 ENST00000427419.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00800
• Publications: 4 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=-0.76).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SLC40A1	ENST00000427419.5	c.-103+344G>A		intron_variant	Intron 1 of 2	1		ENSP00000392730.1
SLC40A1	ENST00000440626.1	c.-64-1034G>A		intron_variant	Intron 1 of 2	1		ENSP00000396134.1
SLC40A1	ENST00000427241.5	c.-102-996G>A		intron_variant	Intron 2 of 7	5		ENSP00000390005.1
SLC40A1	ENST00000455320.5	c.-103+150G>A		intron_variant	Intron 1 of 3	3		ENSP00000413549.1

Frequencies

GnomAD3 genomes AF: 0.0863 AC: 13119 AN: 152026 Hom.: 1116 Cov.: 31

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.0965

Gnomad AMR AF: 0.0522

Gnomad ASJ AF: 0.0404

Gnomad EAS AF: 0.0248

Gnomad SAS AF: 0.0838

Gnomad FIN AF: 0.0188

Gnomad MID AF: 0.108

Gnomad NFE AF: 0.0327

Gnomad OTH AF: 0.0831

GnomAD4 exome AF: 0.0317 AC: 8 AN: 252 Hom.: 1 AF XY: 0.0357 AC XY: 7 AN XY: 196

African (AFR) AF: 0.500 AC: 1 AN: 2

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 4

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2

European-Non Finnish (NFE) AF: 0.0324 AC: 7 AN: 216

Other (OTH) AF: 0.00 AC: 0 AN: 16

GnomAD4 genome AF: 0.0864 AC: 13152 AN: 152144 Hom.: 1118 Cov.: 31 AF XY: 0.0850 AC XY: 6325 AN XY: 74384

African (AFR) AF: 0.216 AC: 8968 AN: 41470

American (AMR) AF: 0.0521 AC: 797 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0404 AC: 140 AN: 3464

East Asian (EAS) AF: 0.0247 AC: 127 AN: 5148

South Asian (SAS) AF: 0.0845 AC: 408 AN: 4828

European-Finnish (FIN) AF: 0.0188 AC: 200 AN: 10614

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0326 AC: 2220 AN: 67996

Other (OTH) AF: 0.0818 AC: 173 AN: 2116

Alfa AF: 0.0574 Hom.: 216

Bravo AF: 0.0953

Asia WGS AF: 0.0630 AC: 218 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	7.1
DANN	Benign	0.80
PhyloP100		-0.0080
PromoterAI		-0.034	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs10202029; hg19: chr2-190446284;