4-17708963-C-T

Position:

• chr4-17708963-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_015688.2(FAM184B):​c.823G>A​(p.Asp275Asn) variant causes a missense change. The variant allele was found at a frequency of 0.00000258 in 1,550,274 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000066 (0 hom., cov: 29)
  • Exomes 𝑓: 0.0000021 (0 hom.)
• Consequence: FAM184B NM_015688.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.78

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.3510232).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM184B	NM_015688.2	c.823G>A	p.Asp275Asn	missense_variant	2/18	ENST00000265018.4	NP_056503.1
FAM184B	XM_047450066.1	c.823G>A	p.Asp275Asn	missense_variant	2/17		XP_047306022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM184B	ENST00000265018.4	c.823G>A	p.Asp275Asn	missense_variant	2/18	1	NM_015688.2	ENSP00000265018.3

Frequencies

GnomAD3 genomes AF: 0.00000658 AC: 1 AN: 151918 Hom.: 0 Cov.: 29

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.00000643 AC: 1 AN: 155496 Hom.: 0 AF XY: 0.0000121 AC XY: 1 AN XY: 82432

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000166

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000215 AC: 3 AN: 1398356 Hom.: 0 Cov.: 30 AF XY: 0.00000145 AC XY: 1 AN XY: 689660

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000185

Gnomad4 OTH exome AF: 0.0000172

GnomAD4 genome AF: 0.00000658 AC: 1 AN: 151918 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 74174

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.27
BayesDel_addAF	Benign	-0.029	T
BayesDel_noAF	Benign	-0.27
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.66
Eigen_PC	Uncertain	0.65
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.84	T
M_CAP	Benign	0.052	D
MetaRNN	Benign	0.35	T
MetaSVM	Uncertain	0.17	D
MutationAssessor	Uncertain	2.5	M
PrimateAI	Uncertain	0.56	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.30
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.024	D
Polyphen		0.99	D
Vest4		0.20
MutPred		0.19		Gain of MoRF binding (P = 0.0359);
MVP		0.44
ClinPred		0.97	D
GERP RS		5.1
Varity_R		0.38
gMVP		0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs61746992; hg19: chr4-17710586;