rs6851427

Variant summary

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

The NM_025074.7(FRAS1):​c.7011G>A​(p.Ala2337=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 1,613,104 control chromosomes in the GnomAD database, including 109,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.33 ( 8800 hom., cov: 31)
Exomes 𝑓: 0.37 ( 100644 hom. )

Consequence

FRAS1
NM_025074.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:7

Conservation

PhyloP100: -2.52
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.82).
BP6
Variant 4-78464565-G-A is Benign according to our data. Variant chr4-78464565-G-A is described in ClinVar as [Benign]. Clinvar id is 261811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78464565-G-A is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=-2.53 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FRAS1NM_025074.7 linkuse as main transcriptc.7011G>A p.Ala2337= synonymous_variant 49/74 ENST00000512123.4 NP_079350.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FRAS1ENST00000512123.4 linkuse as main transcriptc.7011G>A p.Ala2337= synonymous_variant 49/745 NM_025074.7 ENSP00000422834 P1Q86XX4-2
FRAS1ENST00000682513.1 linkuse as main transcriptc.7011G>A p.Ala2337= synonymous_variant 49/64 ENSP00000508201

Frequencies

GnomAD3 genomes
AF:
0.326
AC:
49493
AN:
151860
Hom.:
8787
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.179
Gnomad AMI
AF:
0.380
Gnomad AMR
AF:
0.407
Gnomad ASJ
AF:
0.334
Gnomad EAS
AF:
0.295
Gnomad SAS
AF:
0.303
Gnomad FIN
AF:
0.436
Gnomad MID
AF:
0.250
Gnomad NFE
AF:
0.383
Gnomad OTH
AF:
0.332
GnomAD3 exomes
AF:
0.371
AC:
92053
AN:
248356
Hom.:
17953
AF XY:
0.366
AC XY:
49251
AN XY:
134672
show subpopulations
Gnomad AFR exome
AF:
0.169
Gnomad AMR exome
AF:
0.474
Gnomad ASJ exome
AF:
0.328
Gnomad EAS exome
AF:
0.311
Gnomad SAS exome
AF:
0.304
Gnomad FIN exome
AF:
0.441
Gnomad NFE exome
AF:
0.386
Gnomad OTH exome
AF:
0.351
GnomAD4 exome
AF:
0.367
AC:
536916
AN:
1461126
Hom.:
100644
Cov.:
41
AF XY:
0.366
AC XY:
266054
AN XY:
726828
show subpopulations
Gnomad4 AFR exome
AF:
0.173
Gnomad4 AMR exome
AF:
0.463
Gnomad4 ASJ exome
AF:
0.330
Gnomad4 EAS exome
AF:
0.306
Gnomad4 SAS exome
AF:
0.305
Gnomad4 FIN exome
AF:
0.443
Gnomad4 NFE exome
AF:
0.376
Gnomad4 OTH exome
AF:
0.341
GnomAD4 genome
AF:
0.326
AC:
49534
AN:
151978
Hom.:
8800
Cov.:
31
AF XY:
0.329
AC XY:
24410
AN XY:
74258
show subpopulations
Gnomad4 AFR
AF:
0.179
Gnomad4 AMR
AF:
0.407
Gnomad4 ASJ
AF:
0.334
Gnomad4 EAS
AF:
0.295
Gnomad4 SAS
AF:
0.303
Gnomad4 FIN
AF:
0.436
Gnomad4 NFE
AF:
0.383
Gnomad4 OTH
AF:
0.335
Alfa
AF:
0.363
Hom.:
20357
Bravo
AF:
0.320
Asia WGS
AF:
0.306
AC:
1067
AN:
3476
EpiCase
AF:
0.367
EpiControl
AF:
0.362

ClinVar

Significance: Benign
Submissions summary: Benign:7
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Fraser syndrome 1 Benign:3
Benign, no assertion criteria providedclinical testingDiagnostic Laboratory, Department of Genetics, University Medical Center Groningen-- -
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 13, 2018This 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. -
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabAug 10, 2021- -
not specified Benign:2
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Benign, no assertion criteria providedclinical testingGenome Diagnostics Laboratory, University Medical Center Utrecht-- -
not provided Benign:2
Benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpFeb 01, 2024- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.82
CADD
Benign
0.27
DANN
Benign
0.71

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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.

Other links and lift over

dbSNP: rs6851427; hg19: chr4-79385719; COSMIC: COSV53590139; API