Variant 4-17633777-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015688.2(FAM184B):c.3001A>G(p.Ile1001Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00205 in 1,551,628 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0012 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0021 ( 13 hom. )

Consequence

FAM184B
NM_015688.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.70

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009217709).

BS2

High Homozygotes in GnomAdExome4 at 13 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM184B	NM_015688.2 linkuse as main transcript	c.3001A>G	p.Ile1001Val	missense_variant	17/18	ENST00000265018.4	NP_056503.1	Q9ULE4
MED28	NM_025205.5 linkuse as main transcript	c.*9979T>C		3_prime_UTR_variant	4/4	ENST00000237380.12	NP_079481.2	Q9H204
FAM184B	XM_047450066.1 linkuse as main transcript	c.3001A>G	p.Ile1001Val	missense_variant	17/17		XP_047306022.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM184B	ENST00000265018.4 linkuse as main transcript	c.3001A>G	p.Ile1001Val	missense_variant	17/18	1	NM_015688.2	ENSP00000265018.3		Q9ULE4
MED28	ENST00000237380.12 linkuse as main transcript	c.*9979T>C		3_prime_UTR_variant	4/4	1	NM_025205.5	ENSP00000237380.6		Q9H204

Frequencies

GnomAD3 genomes

AF:

0.00120

AC:

183

AN:

152186

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000362

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000786

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00122

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00206

Gnomad OTH

AF:

0.000956

GnomAD3 exomes

AF:

0.00144

AC:

226

AN:

156714

Hom.:

AF XY:

0.00139

AC XY:

115

AN XY:

82998

show subpopulations

Gnomad AFR exome

AF:

0.000375

Gnomad AMR exome

AF:

0.000527

Gnomad ASJ exome

AF:

0.000235

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000132

Gnomad FIN exome

AF:

0.00226

Gnomad NFE exome

AF:

0.00262

Gnomad OTH exome

AF:

0.00182

GnomAD4 exome

AF:

0.00214

AC:

3000

AN:

1399324

Hom.:

Cov.:

AF XY:

0.00209

AC XY:

1444

AN XY:

690166

show subpopulations

Gnomad4 AFR exome

AF:

0.000411

Gnomad4 AMR exome

AF:

0.000644

Gnomad4 ASJ exome

AF:

0.000159

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000101

Gnomad4 FIN exome

AF:

0.00237

Gnomad4 NFE exome

AF:

0.00254

Gnomad4 OTH exome

AF:

0.00141

GnomAD4 genome

AF:

0.00120

AC:

183

AN:

152304

Hom.:

Cov.:

AF XY:

0.000846

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000361

Gnomad4 AMR

AF:

0.000785

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00122

Gnomad4 NFE

AF:

0.00206

Gnomad4 OTH

AF:

0.000946

Alfa

AF:

0.00211

Hom.:

Bravo

AF:

0.00136

TwinsUK

AF:

0.00324

AC:

ALSPAC

AF:

0.00182

AC:

ExAC

AF:

0.00102

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 15, 2021

The c.3001A>G (p.I1001V) alteration is located in exon 17 (coding exon 17) of the FAM184B gene. This alteration results from a A to G substitution at nucleotide position 3001, causing the isoleucine (I) at amino acid position 1001 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.095

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.54

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

Eigen

Benign

-0.13

Eigen_PC

Benign

-0.19

FATHMM_MKL

Benign

0.58

LIST_S2

Benign

0.71

M_CAP

Benign

0.012

MetaRNN

Benign

0.0092

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-0.60

REVEL

Benign

0.046

Sift

Uncertain

0.010

Sift4G

Pathogenic

0.0

Polyphen

0.72

Vest4

0.21

MVP

0.040

ClinPred

0.016

GERP RS

1.3

Varity_R

0.068

gMVP

0.14

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over