rs10020432

Positions:

• chr4-73455883-A-G

Variant summary

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

The NM_001134.3(AFP):​c.*263A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.572 in 522,616 control chromosomes in the GnomAD database, including 86,663 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 0.54 (22710 hom., cov: 32)
  • Exomes 𝑓: 0.58 (63953 hom.)
• Consequence: AFP NM_001134.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.650

Genes affected

AFP (HGNC:317): (alpha fetoprotein) This gene encodes alpha-fetoprotein, a major plasma protein produced by the yolk sac and the liver during fetal life. Alpha-fetoprotein expression in adults is often associated with hepatocarcinoma and with teratoma, and has prognostic value for managing advanced gastric cancer. However, hereditary persistance of alpha-fetoprotein may also be found in individuals with no obvious pathology. The protein is thought to be the fetal counterpart of serum albumin, and the alpha-fetoprotein and albumin genes are present in tandem in the same transcriptional orientation on chromosome 4. Alpha-fetoprotein is found in monomeric as well as dimeric and trimeric forms, and binds copper, nickel, fatty acids and bilirubin. The level of alpha-fetoprotein in amniotic fluid is used to measure renal loss of protein to screen for spina bifida and anencephaly. [provided by RefSeq, Oct 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AFP	NM_001134.3	c.*263A>G		3_prime_UTR_variant	15/15	ENST00000395792.7	NP_001125.1
AFP	NM_001354717.2	c.*263A>G		3_prime_UTR_variant	16/16		NP_001341646.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AFP	ENST00000395792.7	c.*263A>G		3_prime_UTR_variant	15/15	1	NM_001134.3	ENSP00000379138	P1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82094 AN: 151794 Hom.: 22717 Cov.: 32

Gnomad AFR AF: 0.452

Gnomad AMI AF: 0.607

Gnomad AMR AF: 0.473

Gnomad ASJ AF: 0.448

Gnomad EAS AF: 0.659

Gnomad SAS AF: 0.525

Gnomad FIN AF: 0.571

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.501

GnomAD4 exome AF: 0.585 AC: 216736 AN: 370706 Hom.: 63953 Cov.: 0 AF XY: 0.584 AC XY: 115566 AN XY: 197888

Gnomad4 AFR exome AF: 0.462

Gnomad4 AMR exome AF: 0.485

Gnomad4 ASJ exome AF: 0.459

Gnomad4 EAS exome AF: 0.662

Gnomad4 SAS exome AF: 0.543

Gnomad4 FIN exome AF: 0.586

Gnomad4 NFE exome AF: 0.603

Gnomad4 OTH exome AF: 0.556

GnomAD4 genome AF: 0.540 AC: 82101 AN: 151910 Hom.: 22710 Cov.: 32 AF XY: 0.538 AC XY: 39926 AN XY: 74218

Gnomad4 AFR AF: 0.451

Gnomad4 AMR AF: 0.473

Gnomad4 ASJ AF: 0.448

Gnomad4 EAS AF: 0.659

Gnomad4 SAS AF: 0.525

Gnomad4 FIN AF: 0.571

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.495

Alfa AF: 0.578 Hom.: 11172

Bravo AF: 0.531

Asia WGS AF: 0.539 AC: 1871 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.15
DANN	Benign	0.63

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: rs10020432; hg19: chr4-74321600;