Variant chr4-78057987-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_025074.7(FRAS1):c.-23C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.187 in 1,611,780 control chromosomes in the GnomAD database, including 30,439 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.15 ( 2236 hom., cov: 32)

Exomes 𝑓: 0.19 ( 28203 hom. )

Consequence

FRAS1
NM_025074.7 5_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.707

Variant links:

Genes affected

FRAS1 (HGNC:19185): (Fraser extracellular matrix complex subunit 1) This gene encodes an extracellular matrix protein that appears to function in the regulation of epidermal-basement membrane adhesion and organogenesis during development. Mutations in this gene cause Fraser syndrome, a multisystem malformation that can include craniofacial, urogenital and respiratory system abnormalities. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Oct 2009]

FRAS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 4-78057987-C-T is Benign according to our data. Variant chr4-78057987-C-T is described in ClinVar as [Benign]. Clinvar id is 349649.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78057987-C-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.203 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FRAS1	NM_025074.7 linkuse as main transcript	c.-23C>T		5_prime_UTR_variant	1/74	ENST00000512123.4
FRAS1	NM_001166133.2 linkuse as main transcript	c.-23C>T		5_prime_UTR_variant	1/42

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FRAS1	ENST00000512123.4 linkuse as main transcript	c.-23C>T		5_prime_UTR_variant	1/74	5	NM_025074.7	P1	Q86XX4-2

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23376

AN:

152124

Hom.:

2236

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0578

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.195

Gnomad ASJ

AF:

0.152

Gnomad EAS

AF:

0.0183

Gnomad SAS

AF:

0.104

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.206

Gnomad OTH

AF:

0.155

GnomAD3 exomes

AF:

0.164

AC:

40598

AN:

248250

Hom.:

3902

AF XY:

0.162

AC XY:

21828

AN XY:

134650

show subpopulations

Gnomad AFR exome

AF:

0.0518

Gnomad AMR exome

AF:

0.185

Gnomad ASJ exome

AF:

0.152

Gnomad EAS exome

AF:

0.0188

Gnomad SAS exome

AF:

0.101

Gnomad FIN exome

AF:

0.208

Gnomad NFE exome

AF:

0.204

Gnomad OTH exome

AF:

0.174

GnomAD4 exome

AF:

0.190

AC:

277407

AN:

1459538

Hom.:

28203

Cov.:

AF XY:

0.187

AC XY:

135962

AN XY:

726100

show subpopulations

Gnomad4 AFR exome

AF:

0.0532

Gnomad4 AMR exome

AF:

0.185

Gnomad4 ASJ exome

AF:

0.151

Gnomad4 EAS exome

AF:

0.0194

Gnomad4 SAS exome

AF:

0.101

Gnomad4 FIN exome

AF:

0.203

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.176

GnomAD4 genome

AF:

0.154

AC:

23376

AN:

152242

Hom.:

2236

Cov.:

AF XY:

0.151

AC XY:

11230

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.0577

Gnomad4 AMR

AF:

0.195

Gnomad4 ASJ

AF:

0.152

Gnomad4 EAS

AF:

0.0184

Gnomad4 SAS

AF:

0.104

Gnomad4 FIN

AF:

0.210

Gnomad4 NFE

AF:

0.206

Gnomad4 OTH

AF:

0.154

Alfa

AF:

0.181

Hom.:

793

Bravo

AF:

0.149

Asia WGS

AF:

0.0770

AC:

270

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Fraser syndrome 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

8.4

DANN

Uncertain

0.98

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

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