chr4-99654081-G-C

Variant names:

• chr4-99654081-G-C
• rs1276164322
• NM_001354435.2:c.568C>G
• C4orf54 p.Arg190Gly

Variant summary

Our verdict is

Likely benign

-2 Likely Benign

-7

-6

-1

0

+5

+6

+9

+10

BenignB

Likely BenignLB

UncertainVUS

Likely PathogenicLP

PathogenicP

. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_001354435.2(C4orf54):​c.568C>G​(p.Arg190Gly) 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 1,383,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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. R190R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: C4orf54 NM_001354435.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.50
• Publications: 0 publications found

Genes affected

C4orf54 (HGNC:27741): (chromosome 4 open reading frame 54)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (REVEL=0.015).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001354435.2. 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
	C4orf54	NM_001354435.2	MANE Select	c.568C>G	p.Arg190Gly	missense	Exon 2 of 3	NP_001341364.1	D6RIA3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C4orf54	ENST00000511828.2	TSL:1 MANE Select	c.568C>G	p.Arg190Gly	missense	Exon 2 of 3	ENSP00000427555.1	D6RIA3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.23e-7 AC: 1 AN: 1383842 Hom.: 0 Cov.: 35 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: 0.00 AC: 0 AN: 79236

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

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5698

European-Non Finnish (NFE) AF: 9.27e-7 AC: 1 AN: 1078886

Other (OTH) AF: 0.00 AC: 0 AN: 57902

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.15
DANN	Benign	0.51
DEOGEN2	Benign	0.010	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.0047	N
LIST_S2	Benign	0.36	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.052	T
MetaSVM	Benign	-0.99	T
PhyloP100		-1.5
PROVEAN	Benign	-0.30	N
REVEL	Benign	0.015
Sift	Benign	0.089	T
Sift4G	Benign	0.38	T
Varity_R		0.042
gMVP		0.099
Mutation Taster		=94/6	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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1276164322;

hg19: chr4-100575238;

ACMG debug oncogenicity

ACGS debug oncogenicity

ACMG debug germline