Genetic Variant C4orf54:p.Pro498Pro (chr4-99653155-C-T) – ACMG Classification: Benign (-11 pts)

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

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)

C4orf54 links:

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
C4orf54	NM_001354435.2 link	c.1494G>A	p.Pro498Pro	synonymous_variant	Exon 2 of 3	ENST00000511828.2	NP_001341364.1
C4orf54	XM_373030.12 link	c.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
C4orf54	ENST00000511828.2 link	c.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.:

Cov.:

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.:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00276

Asia WGS

AF:

0.00346

AC:

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over