chr4-99653155-C-T

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001354435.2(C4orf54):​c.1494G>A​(p.Pro498Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00284 in 1,536,180 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 6 hom., cov: 32)
Exomes 𝑓: 0.0028 ( 21 hom. )

Consequence

C4orf54
NM_001354435.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04
Variant links:
Genes affected
C4orf54 (HGNC:27741): (chromosome 4 open reading frame 54)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
Variant 4-99653155-C-T is Benign according to our data. Variant chr4-99653155-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654975.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=1.04 with no splicing effect.
BS2
High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C4orf54NM_001354435.2 linkc.1494G>A p.Pro498Pro synonymous_variant Exon 2 of 3 ENST00000511828.2 NP_001341364.1
C4orf54XM_373030.12 linkc.1593G>A p.Pro531Pro synonymous_variant Exon 2 of 3 XP_373030.5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C4orf54ENST00000511828.2 linkc.1494G>A p.Pro498Pro synonymous_variant Exon 2 of 3 1 NM_001354435.2 ENSP00000427555.1 D6RIA3

Frequencies

GnomAD3 genomes
AF:
0.00283
AC:
430
AN:
152184
Hom.:
6
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000290
Gnomad AMI
AF:
0.0899
Gnomad AMR
AF:
0.00268
Gnomad ASJ
AF:
0.0216
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0112
Gnomad FIN
AF:
0.000565
Gnomad MID
AF:
0.0222
Gnomad NFE
AF:
0.00222
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00430
AC:
580
AN:
134920
Hom.:
7
AF XY:
0.00468
AC XY:
344
AN XY:
73434
show subpopulations
Gnomad AFR exome
AF:
0.000306
Gnomad AMR exome
AF:
0.00131
Gnomad ASJ exome
AF:
0.0219
Gnomad EAS exome
AF:
0.0000950
Gnomad SAS exome
AF:
0.00823
Gnomad FIN exome
AF:
0.000558
Gnomad NFE exome
AF:
0.00292
Gnomad OTH exome
AF:
0.00481
GnomAD4 exome
AF:
0.00284
AC:
3933
AN:
1383878
Hom.:
21
Cov.:
38
AF XY:
0.00307
AC XY:
2098
AN XY:
682880
show subpopulations
Gnomad4 AFR exome
AF:
0.000285
Gnomad4 AMR exome
AF:
0.00112
Gnomad4 ASJ exome
AF:
0.0213
Gnomad4 EAS exome
AF:
0.0000560
Gnomad4 SAS exome
AF:
0.00942
Gnomad4 FIN exome
AF:
0.000530
Gnomad4 NFE exome
AF:
0.00210
Gnomad4 OTH exome
AF:
0.00449
GnomAD4 genome
AF:
0.00280
AC:
427
AN:
152302
Hom.:
6
Cov.:
32
AF XY:
0.00289
AC XY:
215
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.00268
Gnomad4 ASJ
AF:
0.0216
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0112
Gnomad4 FIN
AF:
0.000565
Gnomad4 NFE
AF:
0.00222
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00345
Hom.:
1
Bravo
AF:
0.00276
Asia WGS
AF:
0.00346
AC:
12
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Apr 01, 2022
CeGaT Center for Human Genetics Tuebingen
Significance: Likely benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

C4orf54: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.71
CADD
Benign
9.8
DANN
Benign
0.37

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: rs555671992; hg19: chr4-100574312; API