rs10020432

Variant names:

• chr4-73455883-A-G
• rs10020432
• NM_001134.3:c.*263A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

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]

AFP Gene-Disease associations (from GenCC):

• hereditary persistence of alpha-fetoprotein

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• congenital deficiency in alpha-fetoprotein

  Inheritance: AR Classification: NO_KNOWN Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001134.3. 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
	AFP	NM_001134.3	MANE Select	c.*263A>G		3_prime_UTR	Exon 15 of 15	NP_001125.1	P02771
	AFP	NM_001354717.2		c.*263A>G		3_prime_UTR	Exon 16 of 16	NP_001341646.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AFP	ENST00000395792.7	TSL:1 MANE Select	c.*263A>G		3_prime_UTR	Exon 15 of 15	ENSP00000379138.2	P02771
	AFP	ENST00000226359.2	TSL:5	c.*169A>G		downstream_gene	N/A	ENSP00000226359.2	J3KMX3
	AFP	ENST00000506820.1	TSL:2	n.*106A>G		downstream_gene	N/A

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

African (AFR) AF: 0.462 AC: 4332 AN: 9384

American (AMR) AF: 0.485 AC: 5920 AN: 12210

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 5204 AN: 11338

East Asian (EAS) AF: 0.662 AC: 16875 AN: 25498

South Asian (SAS) AF: 0.543 AC: 20169 AN: 37110

European-Finnish (FIN) AF: 0.586 AC: 13254 AN: 22618

Middle Eastern (MID) AF: 0.487 AC: 801 AN: 1646

European-Non Finnish (NFE) AF: 0.603 AC: 138148 AN: 229246

Other (OTH) AF: 0.556 AC: 12033 AN: 21656

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

African (AFR) AF: 0.451 AC: 18687 AN: 41428

American (AMR) AF: 0.473 AC: 7210 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.448 AC: 1553 AN: 3466

East Asian (EAS) AF: 0.659 AC: 3402 AN: 5162

South Asian (SAS) AF: 0.525 AC: 2524 AN: 4808

European-Finnish (FIN) AF: 0.571 AC: 6024 AN: 10544

Middle Eastern (MID) AF: 0.517 AC: 152 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40955 AN: 67940

Other (OTH) AF: 0.495 AC: 1044 AN: 2108

Alfa AF: 0.554 Hom.: 17209

Bravo AF: 0.531

Asia WGS AF: 0.539 AC: 1871 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.15
DANN	Benign	0.63
PhyloP100		-0.65
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: rs10020432; hg19: chr4-74321600;