Genetic Variant C4orf50:p.Arg158Gln (chr4-6008486-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001364689.3(C4orf50):c.473G>A(p.Arg158Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 397,918 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0093 ( 8 hom., cov: 33)

Exomes 𝑓: 0.012 ( 29 hom. )

Consequence

C4orf50
NM_001364689.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.399

Publications

0 publications found

Variant links:

Genes affected

C4orf50 (HGNC:33766): (chromosome 4 open reading frame 50)

C4orf50 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0061794817).

BP6

Variant 4-6008486-C-T is Benign according to our data. Variant chr4-6008486-C-T is described in ClinVar as Benign. ClinVar VariationId is 2654618.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 8 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364689.3. 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
	C4orf50	NM_001364689.3	MANE Select	c.473G>A	p.Arg158Gln	missense	Exon 3 of 12	NP_001351618.1	Q6ZRC1
	C4orf50	NM_001364690.2		c.426+3344G>A		intron	N/A	NP_001351619.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4orf50	ENST00000711657.1	MANE Select	c.473G>A	p.Arg158Gln	missense	Exon 3 of 12	ENSP00000518823.1	Q6ZRC1
	C4orf50	ENST00000531445.3	TSL:5	c.473G>A	p.Arg158Gln	missense	Exon 25 of 34	ENSP00000437121.2	Q6ZRC1

Frequencies

GnomAD3 genomes

AF:

0.00930

AC:

1414

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00295

Gnomad AMI

AF:

0.00220

Gnomad AMR

AF:

0.00465

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00746

Gnomad FIN

AF:

0.0250

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0133

Gnomad OTH

AF:

0.00717

GnomAD4 exome

AF:

0.0115

AC:

2836

AN:

245764

Hom.:

Cov.:

AF XY:

0.0119

AC XY:

1483

AN XY:

124624

show subpopulations

African (AFR)

AF:

0.00168

AC:

AN:

7136

American (AMR)

AF:

0.00337

AC:

AN:

7414

Ashkenazi Jewish (ASJ)

AF:

0.000109

AC:

AN:

9190

East Asian (EAS)

AF:

0.00

AC:

AN:

22870

South Asian (SAS)

AF:

0.00727

AC:

AN:

3026

European-Finnish (FIN)

AF:

0.0246

AC:

512

AN:

20848

Middle Eastern (MID)

AF:

0.00155

AC:

AN:

1294

European-Non Finnish (NFE)

AF:

0.0133

AC:

2093

AN:

157662

Other (OTH)

AF:

0.0104

AC:

169

AN:

16324

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

166

332

499

665

831

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome 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

GnomAD4 genome

AF:

0.00929

AC:

1413

AN:

152154

Hom.:

Cov.:

AF XY:

0.00953

AC XY:

709

AN XY:

74386

show subpopulations

African (AFR)

AF:

0.00294

AC:

122

AN:

41516

American (AMR)

AF:

0.00464

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00747

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.0250

AC:

265

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0133

AC:

902

AN:

67974

Other (OTH)

AF:

0.00710

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

138

207

276

345

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00680

Hom.:

Bravo

AF:

0.00716

TwinsUK

AF:

0.0113

AC:

ALSPAC

AF:

0.0166

AC:

ClinVar

ClinVar submissions

Significance: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

AlphaMissense

Benign

0.11

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.96

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.57

MetaRNN

Benign

0.0062

PhyloP100

0.40

GERP RS

2.8

gMVP

0.016

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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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