rs6834059

Variant names:

• chr4-73435958-C-G
• rs6834059
• ENST00000513720.5:n.147-1202C>G

Variant summary

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

The ENST00000513720.5(AFP):​n.147-1202C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.233 in 151,858 control chromosomes in the GnomAD database, including 4,374 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 0.23 (4374 hom., cov: 32)
• Consequence: AFP ENST00000513720.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394
• Publications: 4 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.333 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
AFP	ENST00000513720.5	n.147-1202C>G		intron_variant	Intron 1 of 1	1
AFP	ENST00000515675.1	n.267-1202C>G		intron_variant	Intron 2 of 2	1

Frequencies

GnomAD3 genomes AF: 0.233 AC: 35376 AN: 151742 Hom.: 4375 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.287

Gnomad SAS AF: 0.195

Gnomad FIN AF: 0.215

Gnomad MID AF: 0.304

Gnomad NFE AF: 0.217

Gnomad OTH AF: 0.252

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

GnomAD4 genome AF: 0.233 AC: 35399 AN: 151858 Hom.: 4374 Cov.: 32 AF XY: 0.235 AC XY: 17433 AN XY: 74236

African (AFR) AF: 0.219 AC: 9102 AN: 41478

American (AMR) AF: 0.341 AC: 5188 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 847 AN: 3466

East Asian (EAS) AF: 0.286 AC: 1480 AN: 5166

South Asian (SAS) AF: 0.196 AC: 942 AN: 4814

European-Finnish (FIN) AF: 0.215 AC: 2275 AN: 10566

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.217 AC: 14722 AN: 67826

Other (OTH) AF: 0.251 AC: 530 AN: 2112

Alfa AF: 0.225 Hom.: 475

Bravo AF: 0.240

Asia WGS AF: 0.272 AC: 946 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	4.5
DANN	Benign	0.57
PhyloP100		-0.39
PromoterAI		-0.0065	Neutral

Splicing

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

Other links and lift over

dbSNP: rs6834059; hg19: chr4-74301675;