Variant 4-158671796-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

C4orf46 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

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_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.07 with no splicing effect.

BA1

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	Protein
C4orf46	NM_001008393.4 linkuse as main transcript	c.6C>A	p.Ala2=	synonymous_variant	1/2	ENST00000379205.5	NP_001008394.1
C4orf46	NR_077234.2 linkuse as main transcript	n.60+201C>A		intron_variant, non_coding_transcript_variant
C4orf46	NR_077235.2 linkuse as main transcript	n.60+201C>A		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
C4orf46	ENST00000379205.5 linkuse as main transcript	c.6C>A	p.Ala2=	synonymous_variant	1/2	1	NM_001008393.4	ENSP00000368503	P1
C4orf46	ENST00000508836.1 linkuse as main transcript	n.259+201C>A		intron_variant, non_coding_transcript_variant		1
C4orf46	ENST00000508457.1 linkuse as main transcript	c.6C>A	p.Ala2=	synonymous_variant	1/2	5		ENSP00000421533

Frequencies

GnomAD3 genomes

AF:

0.0178

AC:

2707

AN:

152120

Hom.:

Cov.:

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.:

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.:

Cov.:

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

AF:

0.0178

AC:

2713

AN:

152238

Hom.:

Cov.:

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.:

Bravo

AF:

0.0203

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 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.

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