Genetic Variant ENST00000393526.6:c.-15C>T (chr2-96894036-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The ENST00000393526.6(FAM178B):c.-15C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,610,256 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 0.000020 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

FAM178B
ENST00000393526.6 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.69

Publications

1 publications found

Variant links:

Genes affected

FAM178B (HGNC:28036): (family with sequence similarity 178 member B)

FAM178B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.23035628).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000393526.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM178B	NM_001122646.3	MANE Select	c.1666C>T	p.Arg556Trp	missense	Exon 14 of 17	NP_001116118.2	Q8IXR5-3
FAM178B	NM_016490.5		c.-15C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	NP_057574.2
FAM178B	NM_001172667.2		c.43C>T	p.Arg15Trp	missense	Exon 2 of 5	NP_001166138.1	Q8IXR5-4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM178B	ENST00000393526.6	TSL:1	c.-15C>T		5_prime_UTR_premature_start_codon_gain	Exon 2 of 5	ENSP00000377160.2	Q8IXR5-2
FAM178B	ENST00000490605.3	TSL:5 MANE Select	c.1666C>T	p.Arg556Trp	missense	Exon 14 of 17	ENSP00000429896.1	Q8IXR5-3
FAM178B	ENST00000393526.6	TSL:1	c.-15C>T		5_prime_UTR	Exon 2 of 5	ENSP00000377160.2	Q8IXR5-2

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152040

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000725

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000122

AC:

AN:

245260

AF XY:

0.00000752

show subpopulations

Gnomad AFR exome

AF:

0.0000636

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000903

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1458216

Hom.:

Cov.:

AF XY:

0.0000193

AC XY:

AN XY:

725184

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33430

American (AMR)

AF:

0.0000225

AC:

AN:

44474

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26036

East Asian (EAS)

AF:

0.00

AC:

AN:

39618

South Asian (SAS)

AF:

0.0000117

AC:

AN:

85788

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51968

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5754

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1110876

Other (OTH)

AF:

0.0000332

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

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:

0.0000197

AC:

AN:

152040

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74274

show subpopulations

African (AFR)

AF:

0.0000725

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67974

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.542

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:

0.00

Hom.:

Bravo

AF:

0.0000264

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000165

AC:

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

Benign

0.086

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.46

CADD

Benign

(source)

DANN

Uncertain

1.0

Eigen

Benign

-0.15

Eigen_PC

Benign

0.0057

FATHMM_MKL

Benign

0.68

LIST_S2

Benign

0.76

M_CAP

Benign

0.044

MetaRNN

Benign

0.23

MetaSVM

Benign

-0.98

PhyloP100

1.7

PrimateAI

Benign

0.20

PROVEAN

Uncertain

-3.3

REVEL

Benign

0.061

Sift

Benign

0.064

Sift4G

Uncertain

0.0080

Vest4

0.17

MVP

0.49

MPC

0.067

ClinPred

0.86

GERP RS

4.6

RBP_binding_hub_radar

1.0

RBP_regulation_power_radar

2.8

gMVP

0.24

Mutation Taster

=80/20

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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