chr4-73436498-T-A

Position:

• chr4-73436498-T-A

Variant summary

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

The NM_001134.3(AFP):​c.85+151T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.455 in 550,668 control chromosomes in the GnomAD database, including 58,564 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 0.46 (16605 hom., cov: 32)
  • Exomes 𝑓: 0.45 (41959 hom.)
• Consequence: AFP NM_001134.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.176

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.537 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFP	NM_001134.3	c.85+151T>A		intron_variant		ENST00000395792.7
AFP	NM_001354717.2	c.-248+151T>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFP	ENST00000395792.7	c.85+151T>A		intron_variant		1	NM_001134.3	P1
AFP	ENST00000513720.5	n.147-662T>A		intron_variant, non_coding_transcript_variant		1
AFP	ENST00000515675.1	n.267-662T>A		intron_variant, non_coding_transcript_variant		1
AFP	ENST00000226359.2	c.85+151T>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.464 AC: 70197 AN: 151424 Hom.: 16574 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.423

Gnomad AMR AF: 0.547

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.433

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.469

Gnomad MID AF: 0.481

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.489

GnomAD4 exome AF: 0.452 AC: 180465 AN: 399126 Hom.: 41959 AF XY: 0.451 AC XY: 96007 AN XY: 212776

Gnomad4 AFR exome AF: 0.495

Gnomad4 AMR exome AF: 0.553

Gnomad4 ASJ exome AF: 0.557

Gnomad4 EAS exome AF: 0.460

Gnomad4 SAS exome AF: 0.462

Gnomad4 FIN exome AF: 0.470

Gnomad4 NFE exome AF: 0.433

Gnomad4 OTH exome AF: 0.470

GnomAD4 genome AF: 0.464 AC: 70290 AN: 151542 Hom.: 16605 Cov.: 32 AF XY: 0.468 AC XY: 34655 AN XY: 74060

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.547

Gnomad4 ASJ AF: 0.558

Gnomad4 EAS AF: 0.432

Gnomad4 SAS AF: 0.476

Gnomad4 FIN AF: 0.469

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.492

Alfa AF: 0.440 Hom.: 1817

Bravo AF: 0.470

Asia WGS AF: 0.506 AC: 1729 AN: 3412

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	9.8
DANN	Benign	0.68

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: rs3796676; hg19: chr4-74302215;