Genetic Variant C4orf50:p.His1128His (chr4-5988662-G-A) – 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_001364689.3(C4orf50):c.3384C>T(p.His1128His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000381 in 1,536,066 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0017 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00023 ( 1 hom. )

Consequence

C4orf50
NM_001364689.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -3.32

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 -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 4-5988662-G-A is Benign according to our data. Variant chr4-5988662-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2654614.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-3.32 with no splicing effect.

BS2

High Homozygotes in GnomAd4 at 3 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.3384C>T	p.His1128His	synonymous	Exon 6 of 12	NP_001351618.1	Q6ZRC1
	C4orf50	NM_001364690.2		c.2847C>T	p.His949His	synonymous	Exon 5 of 11	NP_001351619.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
C4orf50	ENST00000711657.1	MANE Select	c.3384C>T	p.His1128His	synonymous	Exon 6 of 12	ENSP00000518823.1	Q6ZRC1
C4orf50	ENST00000531445.3	TSL:5	c.3384C>T	p.His1128His	synonymous	Exon 28 of 34	ENSP00000437121.2	Q6ZRC1
C4orf50	ENST00000639345.1	TSL:5	n.1401C>T		non_coding_transcript_exon	Exon 1 of 8	ENSP00000492340.1	A0A1W2PRI9

Frequencies

GnomAD3 genomes

AF:

0.00174

AC:

264

AN:

152108

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00594

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000589

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000882

Gnomad OTH

AF:

0.000958

GnomAD2 exomes

AF:

0.000400

AC:

AN:

134942

AF XY:

0.000286

show subpopulations

Gnomad AFR exome

AF:

0.00571

Gnomad AMR exome

AF:

0.000449

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000113

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000231

AC:

319

AN:

1383840

Hom.:

Cov.:

AF XY:

0.000205

AC XY:

140

AN XY:

682866

show subpopulations

African (AFR)

AF:

0.00573

AC:

181

AN:

31594

American (AMR)

AF:

0.000476

AC:

AN:

35700

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25182

East Asian (EAS)

AF:

0.000112

AC:

AN:

35734

South Asian (SAS)

AF:

0.0000379

AC:

AN:

79236

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33910

Middle Eastern (MID)

AF:

0.00105

AC:

AN:

5696

European-Non Finnish (NFE)

AF:

0.0000658

AC:

AN:

1078884

Other (OTH)

AF:

0.000639

AC:

AN:

57904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

102

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:

0.00175

AC:

266

AN:

152226

Hom.:

Cov.:

AF XY:

0.00177

AC XY:

132

AN XY:

74428

show subpopulations

African (AFR)

AF:

0.00597

AC:

248

AN:

41540

American (AMR)

AF:

0.000588

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5160

South Asian (SAS)

AF:

0.000208

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000882

AC:

AN:

68018

Other (OTH)

AF:

0.000948

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

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:

0.000214

Hom.:

Bravo

AF:

0.00208

Asia WGS

AF:

0.000577

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

-0.87

CADD

Benign

0.043

(source)

DANN

Benign

0.46

PhyloP100

-3.3

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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