chr4-99649939-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.4710G>A​(p.Gln1570Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00123 in 1,532,236 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0011 ( 1 hom., cov: 32)
Exomes 𝑓: 0.0012 ( 6 hom. )

Consequence

C4orf54
NM_001354435.2 synonymous

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.149
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=-0.53).
BP6
Variant 4-99649939-C-T is Benign according to our data. Variant chr4-99649939-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2654969.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=0.149 with no splicing effect.
BS2
High Homozygotes in GnomAdExome4 at 6 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
C4orf54NM_001354435.2 linkc.4710G>A p.Gln1570Gln synonymous_variant Exon 2 of 3 ENST00000511828.2 NP_001341364.1
C4orf54XM_373030.12 linkc.4809G>A p.Gln1603Gln 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.4710G>A p.Gln1570Gln synonymous_variant Exon 2 of 3 1 NM_001354435.2 ENSP00000427555.1 D6RIA3

Frequencies

GnomAD3 genomes
AF:
0.00107
AC:
163
AN:
151652
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000243
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000393
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000284
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00209
Gnomad OTH
AF:
0.000962
GnomAD3 exomes
AF:
0.000787
AC:
103
AN:
130878
Hom.:
2
AF XY:
0.000760
AC XY:
54
AN XY:
71058
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000123
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.000194
Gnomad NFE exome
AF:
0.00191
Gnomad OTH exome
AF:
0.000742
GnomAD4 exome
AF:
0.00124
AC:
1718
AN:
1380466
Hom.:
6
Cov.:
36
AF XY:
0.00126
AC XY:
857
AN XY:
680514
show subpopulations
Gnomad4 AFR exome
AF:
0.0000634
Gnomad4 AMR exome
AF:
0.000168
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000127
Gnomad4 FIN exome
AF:
0.000236
Gnomad4 NFE exome
AF:
0.00154
Gnomad4 OTH exome
AF:
0.000779
GnomAD4 genome
AF:
0.00107
AC:
163
AN:
151770
Hom.:
1
Cov.:
32
AF XY:
0.000916
AC XY:
68
AN XY:
74206
show subpopulations
Gnomad4 AFR
AF:
0.000242
Gnomad4 AMR
AF:
0.000393
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000284
Gnomad4 NFE
AF:
0.00209
Gnomad4 OTH
AF:
0.000951
Alfa
AF:
0.00129
Hom.:
0
Bravo
AF:
0.000914
Asia WGS
AF:
0.000289
AC:
1
AN:
3478

ClinVar

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

Submissions by phenotype

not provided Benign:1
May 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
-0.53
CADD
Benign
4.8
DANN
Benign
0.58

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: rs150236393; hg19: chr4-100571096; API