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

Variant summary

Our verdict is Benign. The variant received -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

Publications

0 publications found

Variant links:

Genes affected

C4orf54 (HGNC:27741): (chromosome 4 open reading frame 54)

C4orf54 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354435.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4orf54	NM_001354435.2	MANE Select	c.1494G>A	p.Pro498Pro	synonymous	Exon 2 of 3	NP_001341364.1	D6RIA3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4orf54	ENST00000511828.2	TSL:1 MANE Select	c.1494G>A	p.Pro498Pro	synonymous	Exon 2 of 3	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

GnomAD2 exomes

AF:

0.00430

AC:

580

AN:

134920

AF XY:

0.00468

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 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

African (AFR)

AF:

0.000285

AC:

AN:

31594

American (AMR)

AF:

0.00112

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.0213

AC:

536

AN:

25180

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35734

South Asian (SAS)

AF:

0.00942

AC:

746

AN:

79230

European-Finnish (FIN)

AF:

0.000530

AC:

AN:

33968

Middle Eastern (MID)

AF:

0.0105

AC:

AN:

5688

European-Non Finnish (NFE)

AF:

0.00210

AC:

2262

AN:

1078880

Other (OTH)

AF:

0.00449

AC:

260

AN:

57904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

276

552

829

1105

1381

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

192

288

384

480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00280

AC:

427

AN:

152302

Hom.:

Cov.:

AF XY:

0.00289

AC XY:

215

AN XY:

74468

show subpopulations

African (AFR)

AF:

0.000289

AC:

AN:

41568

American (AMR)

AF:

0.00268

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0216

AC:

AN:

3472

East Asian (EAS)

AF:

0.000193

AC:

AN:

5172

South Asian (SAS)

AF:

0.0112

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.0136

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00222

AC:

151

AN:

68030

Other (OTH)

AF:

0.000473

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00345

Hom.:

Bravo

AF:

0.00276

Asia WGS

AF:

0.00346

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.71

CADD

Benign

9.8

(source)

DANN

Benign

0.37

PhyloP100

1.0

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over