4-6008486-C-T

Position:

• chr4-6008486-C-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_001364689.3(C4orf50):​c.473G>A​(p.Arg158Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0107 in 397,918 control chromosomes in the GnomAD database, including 37 homozygotes. In-silico tool predicts a benign outcome for this variant. 5/7 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0093 (8 hom., cov: 33)
  • Exomes 𝑓: 0.012 (29 hom.)
• Consequence: C4orf50 NM_001364689.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.399

Genes affected

C4orf50 (HGNC:33766): (chromosome 4 open reading frame 50)

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0061794817).
• BP6: Variant 4-6008486-C-T is Benign according to our data. Variant chr4-6008486-C-T is described in ClinVar as [Benign]. Clinvar id is 2654618.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd4 at 8 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C4orf50	NM_001364689.3	c.473G>A	p.Arg158Gln	missense_variant	3/12		NP_001351618.1
C4orf50	XM_047415663.1	c.473G>A	p.Arg158Gln	missense_variant	3/15		XP_047271619.1
C4orf50	XM_047415664.1	c.473G>A	p.Arg158Gln	missense_variant	3/13		XP_047271620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C4orf50	ENST00000531445.3	c.473G>A	p.Arg158Gln	missense_variant	25/34	5		ENSP00000437121.2

Frequencies

GnomAD3 genomes AF: 0.00930 AC: 1414 AN: 152040 Hom.: 8 Cov.: 33

Gnomad AFR AF: 0.00295

Gnomad AMI AF: 0.00220

Gnomad AMR AF: 0.00465

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00746

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0133

Gnomad OTH AF: 0.00717

GnomAD4 exome AF: 0.0115 AC: 2836 AN: 245764 Hom.: 29 Cov.: 0 AF XY: 0.0119 AC XY: 1483 AN XY: 124624

Gnomad4 AFR exome AF: 0.00168

Gnomad4 AMR exome AF: 0.00337

Gnomad4 ASJ exome AF: 0.000109

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00727

Gnomad4 FIN exome AF: 0.0246

Gnomad4 NFE exome AF: 0.0133

Gnomad4 OTH exome AF: 0.0104

GnomAD4 genome AF: 0.00929 AC: 1413 AN: 152154 Hom.: 8 Cov.: 33 AF XY: 0.00953 AC XY: 709 AN XY: 74386

Gnomad4 AFR AF: 0.00294

Gnomad4 AMR AF: 0.00464

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00747

Gnomad4 FIN AF: 0.0250

Gnomad4 NFE AF: 0.0133

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00680 Hom.: 0

Bravo AF: 0.00716

TwinsUK AF: 0.0113 AC: 42

ALSPAC AF: 0.0166 AC: 64

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

C4orf50: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.96
FATHMM_MKL	Benign	0.38	N
LIST_S2	Benign	0.57	T
MetaRNN	Benign	0.0062	T
GERP RS		2.8
gMVP		0.016

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs548929659; hg19: chr4-6010213;