chr4-99652026-C-G

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001354435.2(C4orf54):​c.2623G>C​(p.Glu875Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0123 in 1,536,122 control chromosomes in the GnomAD database, including 152 homozygotes. In-silico tool predicts a benign outcome for this variant. 9/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0095 ( 12 hom., cov: 32)
Exomes 𝑓: 0.013 ( 140 hom. )

Consequence

C4orf54
NM_001354435.2 missense

Scores

1
2
12

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.98
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 -10 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.00588125).
BP6
Variant 4-99652026-C-G is Benign according to our data. Variant chr4-99652026-C-G is described in ClinVar as [Benign]. Clinvar id is 2654972.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 12 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C4orf54NM_001354435.2 linkc.2623G>C p.Glu875Gln missense_variant Exon 2 of 3 ENST00000511828.2 NP_001341364.1
C4orf54XM_373030.12 linkc.2722G>C p.Glu908Gln missense_variant Exon 2 of 3 XP_373030.5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
C4orf54ENST00000511828.2 linkc.2623G>C p.Glu875Gln missense_variant Exon 2 of 3 1 NM_001354435.2 ENSP00000427555.1 D6RIA3

Frequencies

GnomAD3 genomes
AF:
0.00950
AC:
1446
AN:
152186
Hom.:
11
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00178
Gnomad AMI
AF:
0.00110
Gnomad AMR
AF:
0.0105
Gnomad ASJ
AF:
0.0199
Gnomad EAS
AF:
0.00116
Gnomad SAS
AF:
0.00683
Gnomad FIN
AF:
0.0220
Gnomad MID
AF:
0.00633
Gnomad NFE
AF:
0.0124
Gnomad OTH
AF:
0.0105
GnomAD3 exomes
AF:
0.0100
AC:
1347
AN:
134578
Hom.:
8
AF XY:
0.0107
AC XY:
783
AN XY:
73302
show subpopulations
Gnomad AFR exome
AF:
0.00217
Gnomad AMR exome
AF:
0.00813
Gnomad ASJ exome
AF:
0.0188
Gnomad EAS exome
AF:
0.000762
Gnomad SAS exome
AF:
0.00685
Gnomad FIN exome
AF:
0.0241
Gnomad NFE exome
AF:
0.0118
Gnomad OTH exome
AF:
0.0150
GnomAD4 exome
AF:
0.0126
AC:
17416
AN:
1383818
Hom.:
140
Cov.:
38
AF XY:
0.0124
AC XY:
8458
AN XY:
682848
show subpopulations
Gnomad4 AFR exome
AF:
0.00177
Gnomad4 AMR exome
AF:
0.00829
Gnomad4 ASJ exome
AF:
0.0200
Gnomad4 EAS exome
AF:
0.000532
Gnomad4 SAS exome
AF:
0.00755
Gnomad4 FIN exome
AF:
0.0221
Gnomad4 NFE exome
AF:
0.0133
Gnomad4 OTH exome
AF:
0.0129
GnomAD4 genome
AF:
0.00953
AC:
1451
AN:
152304
Hom.:
12
Cov.:
32
AF XY:
0.00937
AC XY:
698
AN XY:
74472
show subpopulations
Gnomad4 AFR
AF:
0.00178
Gnomad4 AMR
AF:
0.0105
Gnomad4 ASJ
AF:
0.0199
Gnomad4 EAS
AF:
0.00116
Gnomad4 SAS
AF:
0.00663
Gnomad4 FIN
AF:
0.0220
Gnomad4 NFE
AF:
0.0124
Gnomad4 OTH
AF:
0.0132
Alfa
AF:
0.0119
Hom.:
3
Bravo
AF:
0.00832
TwinsUK
AF:
0.0124
AC:
46
ALSPAC
AF:
0.0119
AC:
46
ExAC
AF:
0.00678
AC:
116
Asia WGS
AF:
0.0220
AC:
77
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
Feb 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Benign
Review Status: criteria provided, single submitter
Collection Method: clinical testing

C4orf54: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.33
BayesDel_addAF
Benign
-0.50
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
23
DANN
Uncertain
1.0
DEOGEN2
Benign
0.015
T
Eigen
Benign
0.12
Eigen_PC
Benign
0.16
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Benign
0.57
T
MetaRNN
Benign
0.0059
T
MetaSVM
Benign
-0.89
T
PROVEAN
Benign
0.14
N
REVEL
Benign
0.084
Sift
Uncertain
0.0090
D
Sift4G
Benign
0.12
T
Vest4
0.17
MVP
0.17
ClinPred
0.034
T
GERP RS
4.5
Varity_R
0.14
gMVP
0.21

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: rs17600994; hg19: chr4-100573183; API