4-99649820-C-T

Variant summary

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

The NM_001354435.2(C4orf54):​c.4829G>A​(p.Arg1610His) variant causes a missense change. The variant allele was found at a frequency of 0.000872 in 1,536,028 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0043 ( 3 hom., cov: 32)
Exomes 𝑓: 0.00049 ( 7 hom. )

Consequence

C4orf54
NM_001354435.2 missense

Scores

3
6
6

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.68
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=0.007854253).
BP6
Variant 4-99649820-C-T is Benign according to our data. Variant chr4-99649820-C-T is described in ClinVar as [Benign]. Clinvar id is 2654968.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Homozygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C4orf54NM_001354435.2 linkc.4829G>A p.Arg1610His missense_variant Exon 2 of 3 ENST00000511828.2 NP_001341364.1
C4orf54XM_373030.12 linkc.4928G>A p.Arg1643His 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.4829G>A p.Arg1610His missense_variant Exon 2 of 3 1 NM_001354435.2 ENSP00000427555.1 D6RIA3

Frequencies

GnomAD3 genomes
AF:
0.00431
AC:
655
AN:
152094
Hom.:
3
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0146
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00223
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000414
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000103
Gnomad OTH
AF:
0.00335
GnomAD3 exomes
AF:
0.000981
AC:
132
AN:
134536
Hom.:
2
AF XY:
0.000725
AC XY:
53
AN XY:
73124
show subpopulations
Gnomad AFR exome
AF:
0.0153
Gnomad AMR exome
AF:
0.000736
Gnomad ASJ exome
AF:
0.000241
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000445
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000190
Gnomad OTH exome
AF:
0.000482
GnomAD4 exome
AF:
0.000494
AC:
683
AN:
1383816
Hom.:
7
Cov.:
37
AF XY:
0.000416
AC XY:
284
AN XY:
682788
show subpopulations
Gnomad4 AFR exome
AF:
0.0149
Gnomad4 AMR exome
AF:
0.000981
Gnomad4 ASJ exome
AF:
0.0000794
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000366
Gnomad4 FIN exome
AF:
0.0000294
Gnomad4 NFE exome
AF:
0.0000501
Gnomad4 OTH exome
AF:
0.00149
GnomAD4 genome
AF:
0.00431
AC:
656
AN:
152212
Hom.:
3
Cov.:
32
AF XY:
0.00429
AC XY:
319
AN XY:
74424
show subpopulations
Gnomad4 AFR
AF:
0.0146
Gnomad4 AMR
AF:
0.00222
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000103
Gnomad4 OTH
AF:
0.00331
Alfa
AF:
0.00233
Hom.:
0
Bravo
AF:
0.00553
ExAC
AF:
0.000796
AC:
19
Asia WGS
AF:
0.000289
AC:
1
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
Pathogenic
0.58
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.30
CADD
Pathogenic
28
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.13
T
Eigen
Uncertain
0.31
Eigen_PC
Uncertain
0.37
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Uncertain
0.92
D
MetaRNN
Benign
0.0079
T
MetaSVM
Benign
-0.61
T
PROVEAN
Uncertain
-3.1
D
REVEL
Benign
0.21
Sift
Uncertain
0.0020
D
Sift4G
Uncertain
0.031
D
Vest4
0.44
MVP
0.43
ClinPred
0.037
T
GERP RS
4.3
Varity_R
0.30
gMVP
0.66

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: rs192702357; hg19: chr4-100570977; API