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GeneBe

rs368815693

chr18-50250809-T-C

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1

The NM_145020.5(CFAP53):c.945A>G(p.Gln315=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,614,222 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.00026 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00011 ( 0 hom. )

Consequence

CFAP53
NM_145020.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.165
Variant links:
Genes affected
CFAP53 (HGNC:26530): (cilia and flagella associated protein 53) This gene belongs to the CFAP53 family. It was found to be differentially expressed by the ciliated cells of frog epidermis and in skin fibroblasts from human. Mutations in this gene are associated with visceral heterotaxy-6, which implicates this gene in determination of left-right asymmetric patterning. [provided by RefSeq, Aug 2015]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

PM2
?
    PM2 - Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
Very rare variant in population databases, with high coverage;
BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 18-50250809-T-C is Benign according to our data. Variant chr18-50250809-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 262562.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=0.165 with no splicing effect.
BS1
?
    BS1 - Allele frequency is greater than expected for disorder
Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000263 (40/152344) while in subpopulation EAS AF= 0.00482 (25/5188). AF 95% confidence interval is 0.00335. There are 1 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CFAP53NM_145020.5 linkuse as main transcriptc.945A>G p.Gln315= synonymous_variant 5/8 ENST00000398545.5

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CFAP53ENST00000398545.5 linkuse as main transcriptc.945A>G p.Gln315= synonymous_variant 5/81 NM_145020.5 P1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000256
AC:
39
AN:
152226
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000965
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00462
Gnomad SAS
AF:
0.00145
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000294
Gnomad OTH
AF:
0.000957
GnomAD3 exomes
AF:
0.000353
AC:
88
AN:
249550
Hom.:
1
AF XY:
0.000332
AC XY:
45
AN XY:
135392
show subpopulations
Gnomad AFR exome
AF:
0.000129
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00334
Gnomad SAS exome
AF:
0.000784
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.000330
GnomAD4 exome
AF:
0.000110
AC:
161
AN:
1461878
Hom.:
0
Cov.:
31
AF XY:
0.000114
AC XY:
83
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.000119
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00154
Gnomad4 SAS exome
AF:
0.000475
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000360
Gnomad4 OTH exome
AF:
0.000844
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000263
AC:
40
AN:
152344
Hom.:
1
Cov.:
33
AF XY:
0.000322
AC XY:
24
AN XY:
74504
show subpopulations
Gnomad4 AFR
AF:
0.0000962
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00482
Gnomad4 SAS
AF:
0.00145
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000294
Gnomad4 OTH
AF:
0.000947
Alfa
AF:
0.0000854
Hom.:
0
Bravo
AF:
0.000151
Asia WGS
AF:
0.0150
AC:
52
AN:
3478

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact Sciences-- -
Heterotaxy, visceral, 6, autosomal Benign:1
Benign, criteria provided, single submitterclinical testingInvitaeOct 04, 2022- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.83
Cadd
Benign
5.2
Dann
Benign
0.48

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.

Other links and lift over

dbSNP: rs368815693; hg19: chr18-47777179; COSMIC: COSV68352000; API