chr4-78482528-C-T

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_025074.7(FRAS1):​c.8745C>T​(p.Phe2915Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.205 in 1,612,948 control chromosomes in the GnomAD database, including 37,424 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 4207 hom., cov: 33)
Exomes 𝑓: 0.20 ( 33217 hom. )

Consequence

FRAS1
NM_025074.7 synonymous

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.18
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 -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.3).
BP6
Variant 4-78482528-C-T is Benign according to our data. Variant chr4-78482528-C-T is described in ClinVar as [Benign]. Clinvar id is 261816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr4-78482528-C-T is described in Lovd as [Benign].
BP7
Synonymous conserved (PhyloP=1.18 with no splicing effect.
BA1
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FRAS1NM_025074.7 linkc.8745C>T p.Phe2915Phe synonymous_variant Exon 58 of 74 ENST00000512123.4 NP_079350.5 Q86XX4-2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FRAS1ENST00000512123.4 linkc.8745C>T p.Phe2915Phe synonymous_variant Exon 58 of 74 5 NM_025074.7 ENSP00000422834.2 Q86XX4-2
FRAS1ENST00000682513.1 linkc.8745C>T p.Phe2915Phe synonymous_variant Exon 58 of 64 ENSP00000508201.1 A0A804HL50

Frequencies

GnomAD3 genomes
AF:
0.220
AC:
33423
AN:
152012
Hom.:
4204
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.327
Gnomad AMI
AF:
0.203
Gnomad AMR
AF:
0.153
Gnomad ASJ
AF:
0.122
Gnomad EAS
AF:
0.00366
Gnomad SAS
AF:
0.0569
Gnomad FIN
AF:
0.158
Gnomad MID
AF:
0.0886
Gnomad NFE
AF:
0.214
Gnomad OTH
AF:
0.198
GnomAD3 exomes
AF:
0.163
AC:
40480
AN:
248552
Hom.:
4274
AF XY:
0.159
AC XY:
21422
AN XY:
134798
show subpopulations
Gnomad AFR exome
AF:
0.331
Gnomad AMR exome
AF:
0.0937
Gnomad ASJ exome
AF:
0.128
Gnomad EAS exome
AF:
0.00245
Gnomad SAS exome
AF:
0.0627
Gnomad FIN exome
AF:
0.162
Gnomad NFE exome
AF:
0.216
Gnomad OTH exome
AF:
0.169
GnomAD4 exome
AF:
0.203
AC:
296670
AN:
1460818
Hom.:
33217
Cov.:
34
AF XY:
0.198
AC XY:
143856
AN XY:
726656
show subpopulations
Gnomad4 AFR exome
AF:
0.326
Gnomad4 AMR exome
AF:
0.102
Gnomad4 ASJ exome
AF:
0.125
Gnomad4 EAS exome
AF:
0.00239
Gnomad4 SAS exome
AF:
0.0643
Gnomad4 FIN exome
AF:
0.165
Gnomad4 NFE exome
AF:
0.226
Gnomad4 OTH exome
AF:
0.186
GnomAD4 genome
AF:
0.220
AC:
33457
AN:
152130
Hom.:
4207
Cov.:
33
AF XY:
0.212
AC XY:
15761
AN XY:
74388
show subpopulations
Gnomad4 AFR
AF:
0.327
Gnomad4 AMR
AF:
0.152
Gnomad4 ASJ
AF:
0.122
Gnomad4 EAS
AF:
0.00367
Gnomad4 SAS
AF:
0.0568
Gnomad4 FIN
AF:
0.158
Gnomad4 NFE
AF:
0.214
Gnomad4 OTH
AF:
0.196
Alfa
AF:
0.200
Hom.:
1846
Bravo
AF:
0.223
Asia WGS
AF:
0.0560
AC:
197
AN:
3478
EpiCase
AF:
0.200
EpiControl
AF:
0.206

ClinVar

Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:2
-
Breakthrough Genomics, Breakthrough Genomics
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: not provided

- -

Feb 03, 2025
Labcorp Genetics (formerly Invitae), Labcorp
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

not specified Benign:1
-
PreventionGenetics, part of Exact Sciences
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

- -

Fraser syndrome 1 Benign:1
Jan 13, 2018
Illumina Laboratory Services, Illumina
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

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
-0.30
CADD
Benign
10
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.020
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: rs41327848; hg19: chr4-79403682; COSMIC: COSV53608178; API