Genetic Variant ENST00000513720.5:n.147-1060G>A (chr4-73436100-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000513720.5(AFP):n.147-1060G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000389 in 514,604 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000028 ( 0 hom. )

Consequence

AFP
ENST00000513720.5 intron

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: 0.980

Publications

2 publications found

Variant links:

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

AFP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.44).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AFP	NM_001134.3 link	c.-163G>A		upstream_gene_variant		ENST00000395792.7	NP_001125.1	P02771
AFP	NM_001354717.2 link	c.-495G>A		upstream_gene_variant			NP_001341646.2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AFP	ENST00000513720.5 link	n.147-1060G>A	intron_variant	Intron 1 of 1	1
AFP	ENST00000515675.1 link	n.267-1060G>A	intron_variant	Intron 2 of 2	1
AFP	ENST00000395792.7 link	c.-163G>A	upstream_gene_variant		1	NM_001134.3	ENSP00000379138.2	P02771
AFP	ENST00000226359.2 link	c.-163G>A	upstream_gene_variant		5		ENSP00000226359.2	J3KMX3

Frequencies

GnomAD3 genomes

AF:

0.00000659

AC:

AN:

151718

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000276

AC:

AN:

362886

Hom.:

AF XY:

0.00000519

AC XY:

AN XY:

192624

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

9622

American (AMR)

AF:

0.00

AC:

AN:

12442

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

11746

East Asian (EAS)

AF:

0.00

AC:

AN:

26500

South Asian (SAS)

AF:

0.0000359

AC:

AN:

27892

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30848

Middle Eastern (MID)

AF:

0.00

AC:

AN:

1678

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

220756

Other (OTH)

AF:

0.00

AC:

AN:

21402

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000659

AC:

AN:

151718

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74088

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41314

American (AMR)

AF:

0.00

AC:

AN:

15220

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67874

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Affects

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Alpha-fetoprotein, hereditary persistence of

Other:1

Jan 01, 2004

OMIM

Significance:Affects

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.44

CADD

Benign

(source)

DANN

Benign

0.69

PhyloP100

0.98

PromoterAI

0.0048

Neutral

(source)

Splicing

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over