Variant 8-61576775-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004318.4(ASPH):c.1146G>A(p.Ala382=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0764 in 1,605,954 control chromosomes in the GnomAD database, including 6,151 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.094 ( 925 hom., cov: 32)

Exomes 𝑓: 0.075 ( 5226 hom. )

Consequence

ASPH
NM_004318.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.953

Variant links:

Genes affected

ASPH (HGNC:757): (aspartate beta-hydroxylase) This gene is thought to play an important role in calcium homeostasis. The gene is expressed from two promoters and undergoes extensive alternative splicing. The encoded set of proteins share varying amounts of overlap near their N-termini but have substantial variations in their C-terminal domains resulting in distinct functional properties. The longest isoforms (a and f) include a C-terminal Aspartyl/Asparaginyl beta-hydroxylase domain that hydroxylates aspartic acid or asparagine residues in the epidermal growth factor (EGF)-like domains of some proteins, including protein C, coagulation factors VII, IX, and X, and the complement factors C1R and C1S. Other isoforms differ primarily in the C-terminal sequence and lack the hydroxylase domain, and some have been localized to the endoplasmic and sarcoplasmic reticulum. Some of these isoforms are found in complexes with calsequestrin, triadin, and the ryanodine receptor, and have been shown to regulate calcium release from the sarcoplasmic reticulum. Some isoforms have been implicated in metastasis. [provided by RefSeq, Sep 2009]

ASPH links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.71).

BP6

Variant 8-61576775-C-T is Benign according to our data. Variant chr8-61576775-C-T is described in ClinVar as [Benign]. Clinvar id is 1192481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr8-61576775-C-T is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.953 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.258 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ASPH	NM_004318.4 linkuse as main transcript	c.1146G>A	p.Ala382=	synonymous_variant	16/25	ENST00000379454.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ASPH	ENST00000379454.9 linkuse as main transcript	c.1146G>A	p.Ala382=	synonymous_variant	16/25	1	NM_004318.4	P3	Q12797-1

Frequencies

GnomAD3 genomes

AF:

0.0945

AC:

14371

AN:

152066

Hom.:

920

Cov.:

show subpopulations

Gnomad AFR

AF:

0.136

Gnomad AMI

AF:

0.0505

Gnomad AMR

AF:

0.122

Gnomad ASJ

AF:

0.0836

Gnomad EAS

AF:

0.270

Gnomad SAS

AF:

0.0759

Gnomad FIN

AF:

0.0240

Gnomad MID

AF:

0.0918

Gnomad NFE

AF:

0.0631

Gnomad OTH

AF:

0.0995

GnomAD3 exomes

AF:

0.0887

AC:

22235

AN:

250694

Hom.:

1452

AF XY:

0.0851

AC XY:

11527

AN XY:

135474

show subpopulations

Gnomad AFR exome

AF:

0.138

Gnomad AMR exome

AF:

0.0968

Gnomad ASJ exome

AF:

0.0863

Gnomad EAS exome

AF:

0.269

Gnomad SAS exome

AF:

0.0704

Gnomad FIN exome

AF:

0.0267

Gnomad NFE exome

AF:

0.0672

Gnomad OTH exome

AF:

0.0856

GnomAD4 exome

AF:

0.0745

AC:

108372

AN:

1453770

Hom.:

5226

Cov.:

AF XY:

0.0742

AC XY:

53673

AN XY:

723034

show subpopulations

Gnomad4 AFR exome

AF:

0.134

Gnomad4 AMR exome

AF:

0.0988

Gnomad4 ASJ exome

AF:

0.0851

Gnomad4 EAS exome

AF:

0.276

Gnomad4 SAS exome

AF:

0.0722

Gnomad4 FIN exome

AF:

0.0278

Gnomad4 NFE exome

AF:

0.0662

Gnomad4 OTH exome

AF:

0.0838

GnomAD4 genome

AF:

0.0945

AC:

14378

AN:

152184

Hom.:

925

Cov.:

AF XY:

0.0941

AC XY:

7004

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.136

Gnomad4 AMR

AF:

0.122

Gnomad4 ASJ

AF:

0.0836

Gnomad4 EAS

AF:

0.270

Gnomad4 SAS

AF:

0.0751

Gnomad4 FIN

AF:

0.0240

Gnomad4 NFE

AF:

0.0631

Gnomad4 OTH

AF:

0.0980

Alfa

AF:

0.0767

Hom.:

653

Bravo

AF:

0.105

Asia WGS

AF:

0.139

AC:

484

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 04, 2018	- -

Facial dysmorphism-lens dislocation-anterior segment abnormalities-spontaneous filtering blebs syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.8

DANN

Benign

0.74

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

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