4-158672047-A-G

Position:

• chr4-158672047-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The ENST00000508836.1(C4orf46):​n.209T>C variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00484 in 558,560 control chromosomes in the GnomAD database, including 40 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 (27 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (13 hom.)
• Consequence: C4orf46 ENST00000508836.1 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.809

Genes affected

C4orf46 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BP6: Variant 4-158672047-A-G is Benign according to our data. Variant chr4-158672047-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1194633.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 = 0.0116 (1765/152120) while in subpopulation AFR AF= 0.0377 (1564/41500). AF 95% confidence interval is 0.0361. There are 27 homozygotes in gnomad4. There are 842 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C4orf46	NR_077234.2	n.10T>C		non_coding_transcript_exon_variant	1/2
C4orf46	NR_077235.2	n.10T>C		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C4orf46	ENST00000508836.1	n.209T>C		non_coding_transcript_exon_variant	1/2	1
ETFDH	ENST00000512251.6	n.80A>G		non_coding_transcript_exon_variant	1/2	4

Frequencies

GnomAD3 genomes AF: 0.0115 AC: 1750 AN: 152002 Hom.: 26 Cov.: 32

Gnomad AFR AF: 0.0374

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00720

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000415

Gnomad FIN AF: 0.0000943

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000721

Gnomad OTH AF: 0.0158

GnomAD4 exome AF: 0.00231 AC: 937 AN: 406440 Hom.: 13 Cov.: 2 AF XY: 0.00216 AC XY: 457 AN XY: 211846

Gnomad4 AFR exome AF: 0.0386

Gnomad4 AMR exome AF: 0.00644

Gnomad4 ASJ exome AF: 0.00141

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000136

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000838

Gnomad4 OTH exome AF: 0.00570

GnomAD4 genome AF: 0.0116 AC: 1765 AN: 152120 Hom.: 27 Cov.: 32 AF XY: 0.0113 AC XY: 842 AN XY: 74376

Gnomad4 AFR AF: 0.0377

Gnomad4 AMR AF: 0.00719

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000415

Gnomad4 FIN AF: 0.0000943

Gnomad4 NFE AF: 0.000721

Gnomad4 OTH AF: 0.0157

Alfa AF: 0.00788 Hom.: 1

Bravo AF: 0.0135

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

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	-0.52
CADD	Benign	0.26
DANN	Benign	0.59

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs112645305; hg19: chr4-159593199;