rs61742285

Positions:

• chr4-17639257-C-G
• chr4-17639257-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_015688.2(FAM184B):​c.2659G>C​(p.Glu887Gln) variant causes a missense change. The variant allele was found at a frequency of 0.0224 in 1,551,624 control chromosomes in the GnomAD database, including 500 homozygotes. 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 0.015 (29 hom., cov: 32)
  • Exomes 𝑓: 0.023 (471 hom.)
• Consequence: FAM184B NM_015688.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.32

Genes affected

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

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0059881806).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0152 (2313/152326) while in subpopulation NFE AF= 0.0253 (1722/68026). AF 95% confidence interval is 0.0243. There are 29 homozygotes in gnomad4. There are 1026 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAM184B	NM_015688.2	c.2659G>C	p.Glu887Gln	missense_variant	14/18	ENST00000265018.4
FAM184B	XM_047450066.1	c.2659G>C	p.Glu887Gln	missense_variant	14/17

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAM184B	ENST00000265018.4	c.2659G>C	p.Glu887Gln	missense_variant	14/18	1	NM_015688.2	P1

Frequencies

GnomAD3 genomes AF: 0.0152 AC: 2312 AN: 152208 Hom.: 29 Cov.: 32

Gnomad AFR AF: 0.00480

Gnomad AMI AF: 0.0537

Gnomad AMR AF: 0.00917

Gnomad ASJ AF: 0.0141

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00331

Gnomad FIN AF: 0.0105

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0124

GnomAD3 exomes AF: 0.0134 AC: 2081 AN: 155872 Hom.: 27 AF XY: 0.0135 AC XY: 1115 AN XY: 82686

Gnomad AFR exome AF: 0.00356

Gnomad AMR exome AF: 0.00664

Gnomad ASJ exome AF: 0.0134

Gnomad EAS exome AF: 0.0000918

Gnomad SAS exome AF: 0.00360

Gnomad FIN exome AF: 0.0107

Gnomad NFE exome AF: 0.0241

Gnomad OTH exome AF: 0.0146

GnomAD4 exome AF: 0.0232 AC: 32497 AN: 1399298 Hom.: 471 Cov.: 34 AF XY: 0.0225 AC XY: 15547 AN XY: 690156

Gnomad4 AFR exome AF: 0.00304

Gnomad4 AMR exome AF: 0.00667

Gnomad4 ASJ exome AF: 0.0131

Gnomad4 EAS exome AF: 0.0000839

Gnomad4 SAS exome AF: 0.00380

Gnomad4 FIN exome AF: 0.0123

Gnomad4 NFE exome AF: 0.0278

Gnomad4 OTH exome AF: 0.0164

GnomAD4 genome AF: 0.0152 AC: 2313 AN: 152326 Hom.: 29 Cov.: 32 AF XY: 0.0138 AC XY: 1026 AN XY: 74488

Gnomad4 AFR AF: 0.00479

Gnomad4 AMR AF: 0.00916

Gnomad4 ASJ AF: 0.0141

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00331

Gnomad4 FIN AF: 0.0105

Gnomad4 NFE AF: 0.0253

Gnomad4 OTH AF: 0.0123

Alfa AF: 0.0221 Hom.: 41

Bravo AF: 0.0146

TwinsUK AF: 0.0254 AC: 94

ALSPAC AF: 0.0298 AC: 115

ESP6500AA AF: 0.00361 AC: 5

ESP6500EA AF: 0.0264 AC: 84

ExAC AF: 0.00971 AC: 249

Asia WGS AF: 0.000577 AC: 2 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.38
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.080	T
Eigen	Uncertain	0.37
Eigen_PC	Uncertain	0.40
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.78	T
MetaRNN	Benign	0.0060	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.34	N
REVEL	Benign	0.20
Sift	Benign	0.72	T
Sift4G	Uncertain	0.030	D
Polyphen		1.0	D
Vest4		0.47
ClinPred		0.014	T
GERP RS		5.0
Varity_R		0.22
gMVP		0.18

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: rs61742285; hg19: chr4-17640880;