Menu
GeneBe

4-158671796-G-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BA1

The NM_001008393.4(C4orf46):c.6C>A(p.Ala2=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00342 in 1,538,622 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.018 ( 82 hom., cov: 32)
Exomes 𝑓: 0.0018 ( 62 hom. )

Consequence

C4orf46
NM_001008393.4 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -2.06
Variant links:
Genes affected
C4orf46 (HGNC:27320): (chromosome 4 open reading frame 46) This gene encodes a small, conserved protein of unknown function that is expressed in a variety of tissues. There are pseudogenes for this gene on chromosomes 6, 8, 16, and X. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 4-158671796-G-T is Benign according to our data. Variant chr4-158671796-G-T is described in ClinVar as [Benign]. Clinvar id is 1283566.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-2.07 with no splicing effect.
BA1
?
    BA1 - Allele frequency is >5% in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0589 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
C4orf46NM_001008393.4 linkuse as main transcriptc.6C>A p.Ala2= synonymous_variant 1/2 ENST00000379205.5
C4orf46NR_077234.2 linkuse as main transcriptn.60+201C>A intron_variant, non_coding_transcript_variant
C4orf46NR_077235.2 linkuse as main transcriptn.60+201C>A intron_variant, non_coding_transcript_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
C4orf46ENST00000379205.5 linkuse as main transcriptc.6C>A p.Ala2= synonymous_variant 1/21 NM_001008393.4 P1
C4orf46ENST00000508836.1 linkuse as main transcriptn.259+201C>A intron_variant, non_coding_transcript_variant 1
C4orf46ENST00000508457.1 linkuse as main transcriptc.6C>A p.Ala2= synonymous_variant 1/25

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0178
AC:
2707
AN:
152120
Hom.:
81
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0609
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00792
Gnomad ASJ
AF:
0.00144
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00949
Gnomad NFE
AF:
0.000382
Gnomad OTH
AF:
0.0148
GnomAD3 exomes
AF:
0.00439
AC:
619
AN:
141056
Hom.:
18
AF XY:
0.00306
AC XY:
228
AN XY:
74440
show subpopulations
Gnomad AFR exome
AF:
0.0635
Gnomad AMR exome
AF:
0.00368
Gnomad ASJ exome
AF:
0.000939
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000358
Gnomad OTH exome
AF:
0.00178
GnomAD4 exome
AF:
0.00184
AC:
2550
AN:
1386384
Hom.:
62
Cov.:
31
AF XY:
0.00165
AC XY:
1130
AN XY:
683286
show subpopulations
Gnomad4 AFR exome
AF:
0.0622
Gnomad4 AMR exome
AF:
0.00457
Gnomad4 ASJ exome
AF:
0.000945
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000149
Gnomad4 OTH exome
AF:
0.00434
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.0178
AC:
2713
AN:
152238
Hom.:
82
Cov.:
32
AF XY:
0.0173
AC XY:
1291
AN XY:
74454
show subpopulations
Gnomad4 AFR
AF:
0.0608
Gnomad4 AMR
AF:
0.00791
Gnomad4 ASJ
AF:
0.00144
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000382
Gnomad4 OTH
AF:
0.0147
Alfa
AF:
0.00436
Hom.:
25
Bravo
AF:
0.0203
Asia WGS
AF:
0.00144
AC:
5
AN:
3478

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
Cadd
Benign
1.0
Dann
Benign
0.80

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs4596202; hg19: chr4-159592948; API