Genetic Variant C4orf54:p.Glu306* (chr4-99653733-C-A) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001354435.2(C4orf54):c.916G>T(p.Glu306*) variant causes a stop gained change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0039 in 1,535,216 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0027 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0040 ( 13 hom. )

Consequence

C4orf54
NM_001354435.2 stop_gained

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.10

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 Likely_benign. Variant got -6 ACMG points.

BP6

Variant 4-99653733-C-A is Benign according to our data. Variant chr4-99653733-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 2654976.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
C4orf54	NM_001354435.2 link	c.916G>T	p.Glu306*	stop_gained	Exon 2 of 3	ENST00000511828.2	NP_001341364.1
C4orf54	XM_373030.12 link	c.1015G>T	p.Glu339*	stop_gained	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.916G>T	p.Glu306*	stop_gained	Exon 2 of 3	1	NM_001354435.2	ENSP00000427555.1		D6RIA3

Frequencies

GnomAD3 genomes

AF:

0.00272

AC:

414

AN:

152094

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000749

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.00321

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00145

Gnomad FIN

AF:

0.00510

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00390

Gnomad OTH

AF:

0.00239

GnomAD3 exomes

AF:

0.00230

AC:

307

AN:

133724

Hom.:

AF XY:

0.00239

AC XY:

174

AN XY:

72772

show subpopulations

Gnomad AFR exome

AF:

0.00109

Gnomad AMR exome

AF:

0.000656

Gnomad ASJ exome

AF:

0.000122

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00193

Gnomad FIN exome

AF:

0.00561

Gnomad NFE exome

AF:

0.00382

Gnomad OTH exome

AF:

0.00243

GnomAD4 exome

AF:

0.00403

AC:

5578

AN:

1383004

Hom.:

Cov.:

AF XY:

0.00383

AC XY:

2613

AN XY:

682404

show subpopulations

Gnomad4 AFR exome

AF:

0.000886

Gnomad4 AMR exome

AF:

0.00126

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000280

Gnomad4 SAS exome

AF:

0.00183

Gnomad4 FIN exome

AF:

0.00537

Gnomad4 NFE exome

AF:

0.00462

Gnomad4 OTH exome

AF:

0.00325

GnomAD4 genome

AF:

0.00272

AC:

414

AN:

152212

Hom.:

Cov.:

AF XY:

0.00270

AC XY:

201

AN XY:

74428

show subpopulations

Gnomad4 AFR

AF:

0.000747

Gnomad4 AMR

AF:

0.00320

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00145

Gnomad4 FIN

AF:

0.00510

Gnomad4 NFE

AF:

0.00390

Gnomad4 OTH

AF:

0.00237

Alfa

AF:

0.00290

Hom.:

Bravo

AF:

0.00262

TwinsUK

AF:

0.00297

AC:

ALSPAC

AF:

0.00259

AC:

ExAC

AF:

0.00162

AC:

Asia WGS

AF:

0.000577

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

Jun 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

C4orf54: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Pathogenic

0.30

BayesDel_noAF

Pathogenic

0.65

CADD

Pathogenic

DANN

Uncertain

1.0

Eigen

Pathogenic

1.0

Eigen_PC

Pathogenic

0.84

FATHMM_MKL

Pathogenic

0.97

Vest4

0.21

GERP RS

5.0

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