chr4-17639367-C-A

Variant names:

• chr4-17639367-C-A
• rs758159377
• NM_015688.2:c.2549G>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015688.2(FAM184B):​c.2549G>T​(p.Arg850Leu) 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. 15/22 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. R850Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: FAM184B NM_015688.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.314
• Publications: 0 publications found

Genes affected

FAM184B (HGNC:29235): (family with sequence similarity 184 member B)

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 (MetaRNN=0.062134176).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015688.2. 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
	FAM184B	NM_015688.2	MANE Select	c.2549G>T	p.Arg850Leu	missense	Exon 14 of 18	NP_056503.1	Q9ULE4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM184B	ENST00000265018.4	TSL:1 MANE Select	c.2549G>T	p.Arg850Leu	missense	Exon 14 of 18	ENSP00000265018.3	Q9ULE4
	FAM184B	ENST00000954035.1		c.2438G>T	p.Arg813Leu	missense	Exon 13 of 17	ENSP00000624094.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	10
DANN	Uncertain	0.98
DEOGEN2	Benign	0.068	T
Eigen	Benign	-0.63
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.51	D
LIST_S2	Benign	0.65	T
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.062	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.95	L
PhyloP100		0.31
PrimateAI	Benign	0.28	T
PROVEAN	Benign	-0.98	N
REVEL	Benign	0.030
Sift	Benign	0.20	T
Sift4G	Uncertain	0.035	D
Polyphen		0.010	B
Vest4		0.22
MutPred		0.20		Loss of MoRF binding (P = 0.0312)
MVP		0.092
ClinPred		0.28	T
GERP RS		1.8
Varity_R		0.067
gMVP		0.27
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: rs758159377; hg19: chr4-17640990;