4-5988662-G-T

Variant names:

• chr4-5988662-G-T
• rs113587573
• NM_001364689.3:c.3384C>A

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.3384C>A​(p.His1128Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000723 in 1,383,840 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. H1128H) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: C4orf50 NM_001364689.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.32
• 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=0.104264915).

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.3384C>A	p.His1128Gln	missense	Exon 6 of 12	NP_001351618.1	Q6ZRC1
	C4orf50	NM_001364690.2		c.2847C>A	p.His949Gln	missense	Exon 5 of 11	NP_001351619.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4orf50	ENST00000711657.1	MANE Select	c.3384C>A	p.His1128Gln	missense	Exon 6 of 12	ENSP00000518823.1	Q6ZRC1
	C4orf50	ENST00000531445.3	TSL:5	c.3384C>A	p.His1128Gln	missense	Exon 28 of 34	ENSP00000437121.2	Q6ZRC1
	C4orf50	ENST00000639345.1	TSL:5	n.1401C>A		non_coding_transcript_exon	Exon 1 of 8	ENSP00000492340.1	A0A1W2PRI9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.00 AC: 0 AN: 134942 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383840 Hom.: 0 Cov.: 82 AF XY: 0.00000146 AC XY: 1 AN XY: 682866

African (AFR) AF: 0.00 AC: 0 AN: 31594

American (AMR) AF: 0.00 AC: 0 AN: 35700

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25182

East Asian (EAS) AF: 0.00 AC: 0 AN: 35734

South Asian (SAS) AF: 0.0000126 AC: 1 AN: 79236

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 33910

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078884

Other (OTH) AF: 0.00 AC: 0 AN: 57904

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.0010
DANN	Benign	0.79
Eigen	Benign	-0.98
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.29	T
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.10	T
MetaSVM	Benign	-0.96	T
PhyloP100		-3.3
REVEL	Benign	0.024
MVP		0.081
MPC		0.025
ClinPred		0.077	T
GERP RS		-3.7
gMVP		0.035
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs113587573; hg19: chr4-5990389;