Variant chr4-158671871-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -18 ACMG points: 0P and 18B. BP4_ModerateBP6_Very_StrongBS1BS2

The NM_001008393.4(C4orf46):c.-70C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,312,510 control chromosomes in the GnomAD database, including 60 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 28 hom., cov: 32)

Exomes 𝑓: 0.0016 ( 32 hom. )

Consequence

C4orf46
NM_001008393.4 5_prime_UTR

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.80

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -18 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.33).

BP6

Variant 4-158671871-G-C is Benign according to our data. Variant chr4-158671871-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 1198029.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1773/152152) while in subpopulation AFR AF= 0.0379 (1573/41492). AF 95% confidence interval is 0.0364. There are 28 homozygotes in gnomad4. There are 839 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 28 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	#exon/exons	MANE
C4orf46	NM_001008393.4 linkuse as main transcript	c.-70C>G	5_prime_UTR_variant	1/2	ENST00000379205.5
C4orf46	NR_077234.2 linkuse as main transcript	n.60+126C>G	intron_variant, non_coding_transcript_variant
C4orf46	NR_077235.2 linkuse as main transcript	n.60+126C>G	intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	Effect	#exon/exons	TSL	MANE	Appris
C4orf46	ENST00000379205.5 linkuse as main transcript	c.-70C>G	5_prime_UTR_variant	1/2	1	NM_001008393.4	P1
C4orf46	ENST00000508836.1 linkuse as main transcript	n.259+126C>G	intron_variant, non_coding_transcript_variant		1
C4orf46	ENST00000508457.1 linkuse as main transcript	c.-70C>G	5_prime_UTR_variant	1/2	5

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1758

AN:

152032

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0377

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00714

Gnomad ASJ

AF:

0.000864

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.0000944

Gnomad MID

AF:

0.00955

Gnomad NFE

AF:

0.000720

Gnomad OTH

AF:

0.0158

GnomAD4 exome

AF:

0.00160

AC:

1860

AN:

1160358

Hom.:

Cov.:

AF XY:

0.00153

AC XY:

864

AN XY:

564282

show subpopulations

Gnomad4 AFR exome

AF:

0.0397

Gnomad4 AMR exome

AF:

0.00610

Gnomad4 ASJ exome

AF:

0.00128

Gnomad4 EAS exome

AF:

0.0000325

Gnomad4 SAS exome

AF:

0.000123

Gnomad4 FIN exome

AF:

0.0000231

Gnomad4 NFE exome

AF:

0.000544

Gnomad4 OTH exome

AF:

0.00453

GnomAD4 genome

AF:

0.0117

AC:

1773

AN:

152152

Hom.:

Cov.:

AF XY:

0.0113

AC XY:

839

AN XY:

74370

show subpopulations

Gnomad4 AFR

AF:

0.0379

Gnomad4 AMR

AF:

0.00713

Gnomad4 ASJ

AF:

0.000864

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000415

Gnomad4 FIN

AF:

0.0000944

Gnomad4 NFE

AF:

0.000720

Gnomad4 OTH

AF:

0.0156

Alfa

AF:

0.00784

Hom.:

Bravo

AF:

0.0135

Asia WGS

AF:

0.00433

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Sep 17, 2018	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.33

CADD

Benign

DANN

Benign

0.76

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