rs6834059

Positions:

• chr4-73435958-C-G

Variant summary

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

The ENST00000513720.5(AFP):​n.147-1202C>G variant causes a intron, non coding transcript 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, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.394

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=-0.82).
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFP	ENST00000513720.5	n.147-1202C>G		intron_variant, non_coding_transcript_variant		1
AFP	ENST00000515675.1	n.267-1202C>G		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.341

Gnomad4 ASJ AF: 0.244

Gnomad4 EAS AF: 0.286

Gnomad4 SAS AF: 0.196

Gnomad4 FIN AF: 0.215

Gnomad4 NFE AF: 0.217

Gnomad4 OTH AF: 0.251

Alfa AF: 0.226 Hom.: 361

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs6834059; hg19: chr4-74301675;