Genetic Variant FAM184B:p.Glu887Gln (chr4-17639257-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.32

Publications

7 publications found

Variant links:

Genes affected

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

FAM184B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 29 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM184B	NM_015688.2 link	c.2659G>C	p.Glu887Gln	missense_variant	Exon 14 of 18	ENST00000265018.4	NP_056503.1	Q9ULE4
FAM184B	XM_047450066.1 link	c.2659G>C	p.Glu887Gln	missense_variant	Exon 14 of 17		XP_047306022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM184B	ENST00000265018.4 link	c.2659G>C	p.Glu887Gln	missense_variant	Exon 14 of 18	1	NM_015688.2	ENSP00000265018.3		Q9ULE4

Frequencies

GnomAD3 genomes

AF:

0.0152

AC:

2312

AN:

152208

Hom.:

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0134

AC:

2081

AN:

155872

AF XY:

0.0135

show subpopulations

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 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.:

AF XY:

0.0225

AC XY:

15547

AN XY:

690156

show subpopulations

African (AFR)

AF:

0.00304

AC:

AN:

31590

American (AMR)

AF:

0.00667

AC:

238

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.0131

AC:

331

AN:

25178

East Asian (EAS)

AF:

0.0000839

AC:

AN:

35738

South Asian (SAS)

AF:

0.00380

AC:

301

AN:

79234

European-Finnish (FIN)

AF:

0.0123

AC:

605

AN:

49222

Middle Eastern (MID)

AF:

0.00386

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0278

AC:

29948

AN:

1078942

Other (OTH)

AF:

0.0164

AC:

953

AN:

57994

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

1777

3553

5330

7106

8883

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1164

2328

3492

4656

5820

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0152

AC:

2313

AN:

152326

Hom.:

Cov.:

AF XY:

0.0138

AC XY:

1026

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.00479

AC:

199

AN:

41582

American (AMR)

AF:

0.00916

AC:

140

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.0141

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00331

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.0105

AC:

112

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0253

AC:

1722

AN:

68026

Other (OTH)

AF:

0.0123

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

120

241

361

482

602

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0221

Hom.:

Bravo

AF:

0.0146

TwinsUK

AF:

0.0254

AC:

ALSPAC

AF:

0.0298

AC:

115

ESP6500AA

AF:

0.00361

AC:

ESP6500EA

AF:

0.0264

AC:

ExAC

AF:

0.00971

AC:

249

Asia WGS

AF:

0.000577

AC:

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

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.080

Eigen

Uncertain

0.37

Eigen_PC

Uncertain

0.40

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.78

MetaRNN

Benign

0.0060

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.7

PhyloP100

5.3

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.34

REVEL

Benign

0.20

Sift

Benign

0.72

Sift4G

Uncertain

0.030

Polyphen

1.0

Vest4

0.47

ClinPred

0.014

GERP RS

5.0

Varity_R

0.22

gMVP

0.18

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over