rs774679756

Variant names:

• chr4-17636627-C-A
• rs774679756
• NM_015688.2:c.2685G>T

Your query was ambiguous. Multiple possible variants found:

• chr4-17636627-C-A
• chr4-17636627-C-G

Variant summary

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

The NM_015688.2(FAM184B):​c.2685G>T​(p.Glu895Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,397,736 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Uncertain significance in ClinVar.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: FAM184B NM_015688.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.677
• Publications: 0 publications found

Genes affected

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

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=0.24858317).

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.2685G>T	p.Glu895Asp	missense	Exon 15 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.2685G>T	p.Glu895Asp	missense	Exon 15 of 18	ENSP00000265018.3	Q9ULE4
	FAM184B	ENST00000954035.1		c.2574G>T	p.Glu858Asp	missense	Exon 14 of 17	ENSP00000624094.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.15e-7 AC: 1 AN: 1397736 Hom.: 0 Cov.: 31 AF XY: 0.00000145 AC XY: 1 AN XY: 689430

African (AFR) AF: 0.0000317 AC: 1 AN: 31564

American (AMR) AF: 0.00 AC: 0 AN: 35558

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25110

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.00 AC: 0 AN: 79184

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48296

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5682

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1078654

Other (OTH) AF: 0.00 AC: 0 AN: 57958

GnomAD4 genome Cov.: 33

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	0.12
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.43
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.16	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Benign	0.63	D
LIST_S2	Benign	0.72	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.9	L
PhyloP100		0.68
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.18
Sift	Benign	0.053	T
Sift4G	Pathogenic	0.0	D
Polyphen		1.0	D
Vest4		0.19
MutPred		0.074		Gain of glycosylation at S893 (P = 0.0344)
MVP		0.12
ClinPred		0.98	D
GERP RS		5.2
Varity_R		0.44
gMVP		0.14
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs774679756; hg19: chr4-17638250;