Genetic Variant C4orf54:p.Arg1610His (chr4-99649820-C-T) – ACMG Classification: Benign (-10 pts)

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

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)

C4orf54 links:

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
C4orf54	NM_001354435.2 link	c.4829G>A	p.Arg1610His	missense_variant	Exon 2 of 3	ENST00000511828.2	NP_001341364.1
C4orf54	XM_373030.12 link	c.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
C4orf54	ENST00000511828.2 link	c.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.:

Cov.:

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.:

AF XY:

0.000725

AC XY:

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.:

Cov.:

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.:

Cov.:

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.:

Bravo

AF:

0.00553

ExAC

AF:

0.000796

AC:

Asia WGS

AF:

0.000289

AC:

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

BayesDel_noAF

Benign

-0.30

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.13

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Uncertain

0.92

MetaRNN

Benign

0.0079

MetaSVM

Benign

-0.61

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.21

Sift

Uncertain

0.0020

Sift4G

Uncertain

0.031

Vest4

0.44

MVP

0.43

ClinPred

0.037

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.

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