Genetic Variant NM_015688.2:c.199C>T (chr4-17709587-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_015688.2(FAM184B):c.199C>T(p.Arg67Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00264 in 1,545,308 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0020 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0027 ( 15 hom. )

Consequence

FAM184B
NM_015688.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.89

Publications

6 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 -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006183207).

BP6

Variant 4-17709587-G-A is Benign according to our data. Variant chr4-17709587-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2654690.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 15 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM184B	NM_015688.2 link	c.199C>T	p.Arg67Trp	missense_variant	Exon 2 of 18	ENST00000265018.4	NP_056503.1
FAM184B	XM_047450066.1 link	c.199C>T	p.Arg67Trp	missense_variant	Exon 2 of 17		XP_047306022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM184B	ENST00000265018.4 link	c.199C>T	p.Arg67Trp	missense_variant	Exon 2 of 18	1	NM_015688.2	ENSP00000265018.3

Frequencies

GnomAD3 genomes

AF:

0.00202

AC:

307

AN:

152222

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00164

Gnomad ASJ

AF:

0.00634

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00414

Gnomad FIN

AF:

0.000565

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00317

Gnomad OTH

AF:

0.00144

GnomAD2 exomes

AF:

0.00254

AC:

364

AN:

143202

AF XY:

0.00268

show subpopulations

Gnomad AFR exome

AF:

0.000293

Gnomad AMR exome

AF:

0.000902

Gnomad ASJ exome

AF:

0.00762

Gnomad EAS exome

AF:

0.0000956

Gnomad FIN exome

AF:

0.000743

Gnomad NFE exome

AF:

0.00307

Gnomad OTH exome

AF:

0.00490

GnomAD4 exome

AF:

0.00271

AC:

3775

AN:

1392968

Hom.:

Cov.:

AF XY:

0.00282

AC XY:

1935

AN XY:

686998

show subpopulations

African (AFR)

AF:

0.000415

AC:

AN:

31338

American (AMR)

AF:

0.00103

AC:

AN:

34828

Ashkenazi Jewish (ASJ)

AF:

0.00801

AC:

198

AN:

24712

East Asian (EAS)

AF:

0.0000280

AC:

AN:

35726

South Asian (SAS)

AF:

0.00383

AC:

300

AN:

78258

European-Finnish (FIN)

AF:

0.000914

AC:

AN:

48148

Middle Eastern (MID)

AF:

0.0117

AC:

AN:

5196

European-Non Finnish (NFE)

AF:

0.00269

AC:

2898

AN:

1077028

Other (OTH)

AF:

0.00388

AC:

224

AN:

57734

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

220

440

660

880

1100

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

108

216

324

432

540

<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:

0.00202

AC:

307

AN:

152340

Hom.:

Cov.:

AF XY:

0.00201

AC XY:

150

AN XY:

74490

show subpopulations

African (AFR)

AF:

0.000361

AC:

AN:

41580

American (AMR)

AF:

0.00163

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.00634

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.00414

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.000565

AC:

AN:

10622

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00317

AC:

216

AN:

68034

Other (OTH)

AF:

0.00142

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00284

Hom.:

Bravo

AF:

0.00211

TwinsUK

AF:

0.00189

AC:

ALSPAC

AF:

0.00234

AC:

ExAC

AF:

0.00240

AC:

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FAM184B: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.11

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.34

Eigen

Benign

0.044

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.47

LIST_S2

Uncertain

0.87

M_CAP

Uncertain

0.18

MetaRNN

Benign

0.0062

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.2

PhyloP100

1.9

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-5.0

REVEL

Uncertain

0.37

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0040

Polyphen

1.0

Vest4

0.27

MVP

0.36

ClinPred

0.045

GERP RS

1.1

Varity_R

0.34

gMVP

0.41

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

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over