Genetic Variant NM_015688.2:c.2920G>A (chr4-17633858-C-T) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_015688.2(FAM184B):c.2920G>A(p.Val974Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000168 in 1,550,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000072 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000011 ( 0 hom. )

Consequence

FAM184B
NM_015688.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23

Publications

2 publications found

Variant links:

Genes affected

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

FAM184B links:

MED28 (HGNC:24628): (mediator complex subunit 28) Predicted to enable actin binding activity. Predicted to act upstream of or within negative regulation of smooth muscle cell differentiation and stem cell population maintenance. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

MED28 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.16558427).

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.2920G>A	p.Val974Met	missense	Exon 17 of 18	NP_056503.1	Q9ULE4
	MED28	NM_025205.5	MANE Select	c.*10060C>T		3_prime_UTR	Exon 4 of 4	NP_079481.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM184B	ENST00000265018.4	TSL:1 MANE Select	c.2920G>A	p.Val974Met	missense	Exon 17 of 18	ENSP00000265018.3	Q9ULE4
MED28	ENST00000237380.12	TSL:1 MANE Select	c.*10060C>T		3_prime_UTR	Exon 4 of 4	ENSP00000237380.6	Q9H204
FAM184B	ENST00000954035.1		c.2809G>A	p.Val937Met	missense	Exon 16 of 17	ENSP00000624094.1

Frequencies

GnomAD3 genomes

AF:

0.0000723

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000524

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000128

AC:

AN:

156414

AF XY:

0.0000121

show subpopulations

Gnomad AFR exome

AF:

0.000121

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000595

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000107

AC:

AN:

1398442

Hom.:

Cov.:

AF XY:

0.0000101

AC XY:

AN XY:

689748

show subpopulations

African (AFR)

AF:

0.0000317

AC:

AN:

31558

American (AMR)

AF:

0.0000562

AC:

AN:

35578

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25156

East Asian (EAS)

AF:

0.00

AC:

AN:

35694

South Asian (SAS)

AF:

0.00

AC:

AN:

79122

European-Finnish (FIN)

AF:

0.0000406

AC:

AN:

49272

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5526

European-Non Finnish (NFE)

AF:

0.00000834

AC:

AN:

1078604

Other (OTH)

AF:

0.0000173

AC:

AN:

57932

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.495

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000722

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.0000481

AC:

AN:

41562

American (AMR)

AF:

0.000523

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.0000943

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68026

Other (OTH)

AF:

0.00

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.539

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:

0.0000386

Hom.:

Bravo

AF:

0.0000982

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.69

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

(source)

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.057

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.68

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.86

M_CAP

Benign

0.026

MetaRNN

Benign

0.17

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.5

PhyloP100

3.2

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-0.82

REVEL

Benign

0.091

Sift

Benign

0.046

Sift4G

Uncertain

0.0080

Polyphen

1.0

Vest4

0.43

MVP

0.13

ClinPred

0.51

GERP RS

5.5

Varity_R

0.077

gMVP

0.40

Mutation Taster

=84/16

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over