dbSNP rs553700628: FAM81B:p.Ile178Val (chr5-95414185-A-G) – 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_152548.3(FAM81B):c.532A>G(p.Ile178Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000346 in 1,605,582 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00036 ( 3 hom. )

Consequence

FAM81B
NM_152548.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.65

Publications

1 publications found

Variant links:

Genes affected

FAM81B (HGNC:26335): (family with sequence similarity 81 member B) Located in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

FAM81B 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=0.0068792105).

BP6

Variant 5-95414185-A-G is Benign according to our data. Variant chr5-95414185-A-G is described in ClinVar as Likely_benign. ClinVar VariationId is 2655593.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152548.3. 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
	FAM81B	NM_152548.3	MANE Select	c.532A>G	p.Ile178Val	missense	Exon 4 of 10	NP_689761.2	Q96LP2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FAM81B	ENST00000283357.10	TSL:1 MANE Select	c.532A>G	p.Ile178Val	missense	Exon 4 of 10	ENSP00000283357.5	Q96LP2
FAM81B	ENST00000507832.5	TSL:1	n.379A>G		non_coding_transcript_exon	Exon 3 of 11	ENSP00000423016.1	H0Y947
FAM81B	ENST00000503099.1	TSL:3	n.*189A>G		non_coding_transcript_exon	Exon 3 of 5	ENSP00000423296.1	H0Y979

Frequencies

GnomAD3 genomes

AF:

0.000235

AC:

AN:

149052

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000248

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000672

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00612

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000299

Gnomad OTH

AF:

0.00101

GnomAD2 exomes

AF:

0.000693

AC:

167

AN:

241000

AF XY:

0.000887

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000306

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000468

Gnomad NFE exome

AF:

0.000191

Gnomad OTH exome

AF:

0.000521

GnomAD4 exome

AF:

0.000358

AC:

521

AN:

1456414

Hom.:

Cov.:

AF XY:

0.000514

AC XY:

372

AN XY:

724184

show subpopulations

African (AFR)

AF:

0.0000302

AC:

AN:

33104

American (AMR)

AF:

0.0000230

AC:

AN:

43550

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25834

East Asian (EAS)

AF:

0.00

AC:

AN:

39646

South Asian (SAS)

AF:

0.00456

AC:

388

AN:

85058

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53356

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5728

European-Non Finnish (NFE)

AF:

0.0000919

AC:

102

AN:

1110026

Other (OTH)

AF:

0.000482

AC:

AN:

60112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

111

139

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:

0.000235

AC:

AN:

149168

Hom.:

Cov.:

AF XY:

0.000329

AC XY:

AN XY:

72896

show subpopulations

African (AFR)

AF:

0.0000247

AC:

AN:

40496

American (AMR)

AF:

0.0000672

AC:

AN:

14890

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3380

East Asian (EAS)

AF:

0.00

AC:

AN:

5162

South Asian (SAS)

AF:

0.00612

AC:

AN:

4738

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10390

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000299

AC:

AN:

66924

Other (OTH)

AF:

0.000995

AC:

AN:

2010

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

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:

0.0000908

Hom.:

Bravo

AF:

0.0000680

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ExAC

AF:

0.000852

AC:

103

Asia WGS

AF:

0.00289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

(source)

DANN

Benign

0.85

Eigen

Uncertain

0.62

Eigen_PC

Uncertain

0.64

FATHMM_MKL

Uncertain

0.97

MetaRNN

Benign

0.0069

MetaSVM

Benign

-0.87

PhyloP100

7.7

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.76

REVEL

Benign

0.16

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.037

Vest4

0.57

MVP

0.42

MPC

0.38

ClinPred

0.096

GERP RS

5.5

gMVP

0.38

Mutation Taster

=97/3

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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