Variant 4-73447452-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_001134.3(AFP):c.844-10T>C variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 1 in 1,579,772 control chromosomes in the GnomAD database, including 789,195 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 1.0 ( 75685 hom., cov: 29)

Exomes 𝑓: 1.0 ( 713510 hom. )

Consequence

AFP
NM_001134.3 splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.0004008

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.858

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 4-73447452-T-C is Benign according to our data. Variant chr4-73447452-T-C is described in ClinVar as [Benign]. Clinvar id is 3059552.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr4-73447452-T-C is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.994 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AFP	NM_001134.3 linkuse as main transcript	c.844-10T>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000395792.7
AFP	NM_001354717.2 linkuse as main transcript	c.370-10T>C		splice_polypyrimidine_tract_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AFP	ENST00000395792.7 linkuse as main transcript	c.844-10T>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_001134.3	P1
AFP	ENST00000226359.2 linkuse as main transcript	c.844-10T>C		splice_polypyrimidine_tract_variant, intron_variant		5

Frequencies

GnomAD3 genomes

AF:

0.998

AC:

151599

AN:

151954

Hom.:

75625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.992

Gnomad AMI

AF:

1.00

Gnomad AMR

AF:

0.998

Gnomad ASJ

AF:

1.00

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

1.00

Gnomad FIN

AF:

1.00

Gnomad MID

AF:

1.00

Gnomad NFE

AF:

1.00

Gnomad OTH

AF:

0.998

GnomAD3 exomes

AF:

0.999

AC:

239152

AN:

239278

Hom.:

119513

AF XY:

1.00

AC XY:

129992

AN XY:

130040

show subpopulations

Gnomad AFR exome

AF:

0.993

Gnomad AMR exome

AF:

0.999

Gnomad ASJ exome

AF:

1.00

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

1.00

Gnomad FIN exome

AF:

1.00

Gnomad NFE exome

AF:

1.00

Gnomad OTH exome

AF:

1.00

GnomAD4 exome

AF:

1.00

AC:

1427360

AN:

1427700

Hom.:

713510

Cov.:

AF XY:

1.00

AC XY:

711128

AN XY:

711264

show subpopulations

Gnomad4 AFR exome

AF:

0.992

Gnomad4 AMR exome

AF:

0.999

Gnomad4 ASJ exome

AF:

1.00

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

1.00

Gnomad4 FIN exome

AF:

1.00

Gnomad4 NFE exome

AF:

1.00

Gnomad4 OTH exome

AF:

1.00

GnomAD4 genome

AF:

0.998

AC:

151718

AN:

152072

Hom.:

75685

Cov.:

AF XY:

0.998

AC XY:

74166

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.992

Gnomad4 AMR

AF:

0.998

Gnomad4 ASJ

AF:

1.00

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

1.00

Gnomad4 FIN

AF:

1.00

Gnomad4 NFE

AF:

1.00

Gnomad4 OTH

AF:

0.998

Alfa

AF:

0.999

Hom.:

31137

Bravo

AF:

0.997

Asia WGS

AF:

0.998

AC:

3470

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

AFP-related disorder

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

2.6

DANN

Benign

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00040

dbscSNV1_RF

Benign

0.034

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over