chr4-6008486-C-A

Variant names:

• chr4-6008486-C-A
• rs548929659
• NM_001364689.3:c.473G>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001364689.3(C4orf50):​c.473G>T​(p.Arg158Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 6/8 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R158Q) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: C4orf50 NM_001364689.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.399
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.16773698).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001364689.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4orf50	NM_001364689.3	MANE Select	c.473G>T	p.Arg158Leu	missense	Exon 3 of 12	NP_001351618.1	Q6ZRC1
	C4orf50	NM_001364690.2		c.426+3344G>T		intron	N/A	NP_001351619.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4orf50	ENST00000711657.1	MANE Select	c.473G>T	p.Arg158Leu	missense	Exon 3 of 12	ENSP00000518823.1	Q6ZRC1
	C4orf50	ENST00000531445.3	TSL:5	c.473G>T	p.Arg158Leu	missense	Exon 25 of 34	ENSP00000437121.2	Q6ZRC1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 245764 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 124624

African (AFR) AF: 0.00 AC: 0 AN: 7136

American (AMR) AF: 0.00 AC: 0 AN: 7414

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 9190

East Asian (EAS) AF: 0.00 AC: 0 AN: 22870

South Asian (SAS) AF: 0.00 AC: 0 AN: 3026

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 20848

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 157662

Other (OTH) AF: 0.00 AC: 0 AN: 16324

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_noAF	Benign	-0.32
CADD	Benign	19
DANN	Benign	0.92
FATHMM_MKL	Benign	0.62	D
LIST_S2	Benign	0.51	T
MetaRNN	Benign	0.17	T
PhyloP100		0.40
GERP RS		2.8
gMVP		0.032

Splicing

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

Other links and lift over

dbSNP: rs548929659; hg19: chr4-6010213;