Genetic Variant NM_001394345.1:c.428A>G (chr1-222750009-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001394345.1(FAM177B):c.428A>G(p.Gln143Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.81 in 1,613,604 control chromosomes in the GnomAD database, including 529,331 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.80 ( 48637 hom., cov: 31)

Exomes 𝑓: 0.81 ( 480694 hom. )

Consequence

FAM177B
NM_001394345.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.37

Publications

46 publications found

Variant links:

Genes affected

FAM177B (HGNC:34395): (family with sequence similarity 177 member B)

FAM177B links:

ENSG00000287684 (HGNC:):

ENSG00000287684 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=9.036132E-7).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM177B	NM_001394345.1 link	c.428A>G	p.Gln143Arg	missense_variant	Exon 6 of 6	ENST00000445590.4	NP_001381274.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM177B	ENST00000445590.4 link	c.428A>G	p.Gln143Arg	missense_variant	Exon 6 of 6	5	NM_001394345.1	ENSP00000414451.2		A6PVY3-1

Frequencies

GnomAD3 genomes

AF:

0.799

AC:

121368

AN:

151948

Hom.:

48591

Cov.:

show subpopulations

Gnomad AFR

AF:

0.768

Gnomad AMI

AF:

0.822

Gnomad AMR

AF:

0.838

Gnomad ASJ

AF:

0.726

Gnomad EAS

AF:

0.795

Gnomad SAS

AF:

0.769

Gnomad FIN

AF:

0.797

Gnomad MID

AF:

0.741

Gnomad NFE

AF:

0.816

Gnomad OTH

AF:

0.777

GnomAD2 exomes

AF:

0.806

AC:

200815

AN:

249298

AF XY:

0.802

show subpopulations

Gnomad AFR exome

AF:

0.764

Gnomad AMR exome

AF:

0.857

Gnomad ASJ exome

AF:

0.726

Gnomad EAS exome

AF:

0.785

Gnomad FIN exome

AF:

0.801

Gnomad NFE exome

AF:

0.817

Gnomad OTH exome

AF:

0.777

GnomAD4 exome

AF:

0.811

AC:

1184849

AN:

1461538

Hom.:

480694

Cov.:

AF XY:

0.809

AC XY:

588369

AN XY:

727090

show subpopulations

African (AFR)

AF:

0.764

AC:

25577

AN:

33464

American (AMR)

AF:

0.850

AC:

38000

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.734

AC:

19192

AN:

26130

East Asian (EAS)

AF:

0.817

AC:

32446

AN:

39696

South Asian (SAS)

AF:

0.776

AC:

66950

AN:

86248

European-Finnish (FIN)

AF:

0.801

AC:

42765

AN:

53420

Middle Eastern (MID)

AF:

0.744

AC:

4272

AN:

5744

European-Non Finnish (NFE)

AF:

0.816

AC:

907692

AN:

1111756

Other (OTH)

AF:

0.794

AC:

47955

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.473

Heterozygous variant carriers

11913

23826

35740

47653

59566

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

20906

41812

62718

83624

104530

<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:

0.799

AC:

121471

AN:

152066

Hom.:

48637

Cov.:

AF XY:

0.799

AC XY:

59360

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.768

AC:

31838

AN:

41466

American (AMR)

AF:

0.839

AC:

12815

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.726

AC:

2519

AN:

3468

East Asian (EAS)

AF:

0.796

AC:

4094

AN:

5146

South Asian (SAS)

AF:

0.770

AC:

3704

AN:

4812

European-Finnish (FIN)

AF:

0.797

AC:

8430

AN:

10576

Middle Eastern (MID)

AF:

0.745

AC:

219

AN:

294

European-Non Finnish (NFE)

AF:

0.816

AC:

55461

AN:

67994

Other (OTH)

AF:

0.776

AC:

1641

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1263

2526

3789

5052

6315

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

878

1756

2634

3512

4390

<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:

0.809

Hom.:

225754

Bravo

AF:

0.800

TwinsUK

AF:

0.810

AC:

3003

ALSPAC

AF:

0.830

AC:

3199

ESP6500AA

AF:

0.767

AC:

3039

ESP6500EA

AF:

0.810

AC:

6775

ExAC

AF:

0.803

AC:

97041

Asia WGS

AF:

0.762

AC:

2648

AN:

3478

EpiCase

AF:

0.809

EpiControl

AF:

0.810

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.85

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.023

(source)

DANN

Benign

0.62

DEOGEN2

Benign

0.0084

T;T

Eigen

Benign

-2.4

Eigen_PC

Benign

-2.5

FATHMM_MKL

Benign

0.0048

LIST_S2

Benign

0.092

.;T

MetaRNN

Benign

9.0e-7

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.66

N;N

PhyloP100

-2.4

PrimateAI

Benign

0.18

PROVEAN

Benign

0.25

N;N

REVEL

Benign

0.037

Sift

Benign

1.0

T;T

Sift4G

Benign

0.47

T;T

Polyphen

0.0

B;B

Vest4

0.010

MPC

0.17

ClinPred

0.023

GERP RS

-11

Varity_R

0.025

gMVP

0.031

Mutation Taster

=100/0

polymorphism (auto)

(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