4-158671871-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

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
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.80

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]

ACMG classification

Verdict is Benign. Variant got -12 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_single_submitter, 1 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 GnomAd at 27 AR gene

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1758 AN: 152032 Hom.: 27 Cov.: 32

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.: 32 Cov.: 16 AF XY: 0.00153 AC XY: 864 AN XY: 564282

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.: 28 Cov.: 32 AF XY: 0.0113 AC XY: 839 AN XY: 74370

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.: 1

Bravo AF: 0.0135

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 17, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.33
Cadd	Benign	17
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

Other links and lift over

dbSNP: rs112468926; hg19: chr4-159593023;