Variant rs548267943 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_025074.7(FRAS1):c.109-15del 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 0.0106 in 1,584,726 control chromosomes in the GnomAD database, including 113 homozygotes. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0083 ( 6 hom., cov: 32)

Exomes 𝑓: 0.011 ( 107 hom. )

Consequence

FRAS1
NM_025074.7 splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.377

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 4-78237493-CT-C is Benign according to our data. Variant chr4-78237493-CT-C is described in ClinVar as [Likely_benign]. Clinvar id is 261800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00832 (1267/152202) while in subpopulation NFE AF= 0.0127 (864/68004). AF 95% confidence interval is 0.012. There are 6 homozygotes in gnomad4. There are 629 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 6 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FRAS1	NM_025074.7 linkuse as main transcript	c.109-15del		splice_polypyrimidine_tract_variant, intron_variant		ENST00000512123.4	NP_079350.5
FRAS1	NM_001166133.2 linkuse as main transcript	c.109-15del		splice_polypyrimidine_tract_variant, intron_variant			NP_001159605.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FRAS1	ENST00000512123.4 linkuse as main transcript	c.109-15del		splice_polypyrimidine_tract_variant, intron_variant		5	NM_025074.7	ENSP00000422834	P1	Q86XX4-2

Frequencies

GnomAD3 genomes

AF:

0.00832

AC:

1265

AN:

152084

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00212

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00387

Gnomad ASJ

AF:

0.0135

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00270

Gnomad FIN

AF:

0.0174

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.0127

Gnomad OTH

AF:

0.00479

GnomAD3 exomes

AF:

0.00932

AC:

2317

AN:

248640

Hom.:

AF XY:

0.00951

AC XY:

1283

AN XY:

134906

show subpopulations

Gnomad AFR exome

AF:

0.00162

Gnomad AMR exome

AF:

0.00332

Gnomad ASJ exome

AF:

0.00946

Gnomad EAS exome

AF:

0.000223

Gnomad SAS exome

AF:

0.00266

Gnomad FIN exome

AF:

0.0153

Gnomad NFE exome

AF:

0.0144

Gnomad OTH exome

AF:

0.00797

GnomAD4 exome

AF:

0.0108

AC:

15495

AN:

1432524

Hom.:

107

Cov.:

AF XY:

0.0107

AC XY:

7617

AN XY:

714582

show subpopulations

Gnomad4 AFR exome

AF:

0.00173

Gnomad4 AMR exome

AF:

0.00336

Gnomad4 ASJ exome

AF:

0.00926

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.00302

Gnomad4 FIN exome

AF:

0.0155

Gnomad4 NFE exome

AF:

0.0124

Gnomad4 OTH exome

AF:

0.00877

GnomAD4 genome

AF:

0.00832

AC:

1267

AN:

152202

Hom.:

Cov.:

AF XY:

0.00845

AC XY:

629

AN XY:

74418

show subpopulations

Gnomad4 AFR

AF:

0.00212

Gnomad4 AMR

AF:

0.00386

Gnomad4 ASJ

AF:

0.0135

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00291

Gnomad4 FIN

AF:

0.0174

Gnomad4 NFE

AF:

0.0127

Gnomad4 OTH

AF:

0.00474

Alfa

AF:

0.0102

Hom.:

Bravo

AF:

0.00727

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign/Likely 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	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Likely benign, criteria provided, single submitter	clinical testing	Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	Sep 18, 2017	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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