Variant 8-22096433-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022749.7(FHIP2B):c.221G>A(p.Gly74Asp) variant causes a missense change. The variant allele was found at a frequency of 0.00021 in 1,556,128 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00019 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00021 ( 0 hom. )

Consequence

FHIP2B
NM_022749.7 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.09

Variant links:

Genes affected

FHIP2B (HGNC:16492): (FHF complex subunit HOOK interacting protein 2B)

FHIP2B links:

FHIP2B (HGNC:):

FHIP2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.045322716).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIP2B	NM_022749.7 linkuse as main transcript	c.221G>A	p.Gly74Asp	missense_variant	3/17	ENST00000289921.8	NP_073586.5	Q86V87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIP2B	ENST00000289921.8 linkuse as main transcript	c.221G>A	p.Gly74Asp	missense_variant	3/17	5	NM_022749.7	ENSP00000289921.6		Q86V87

Frequencies

GnomAD3 genomes

AF:

0.000190

AC:

AN:

152264

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000196

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000265

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000210

AC:

AN:

161534

Hom.:

AF XY:

0.000292

AC XY:

AN XY:

85758

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000402

Gnomad ASJ exome

AF:

0.000931

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000219

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000248

Gnomad OTH exome

AF:

0.000899

GnomAD4 exome

AF:

0.000212

AC:

298

AN:

1403746

Hom.:

Cov.:

AF XY:

0.000225

AC XY:

156

AN XY:

692846

show subpopulations

Gnomad4 AFR exome

AF:

0.0000942

Gnomad4 AMR exome

AF:

0.0000830

Gnomad4 ASJ exome

AF:

0.000951

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000214

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000195

Gnomad4 OTH exome

AF:

0.000464

GnomAD4 genome

AF:

0.000190

AC:

AN:

152382

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74524

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.000196

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000265

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000259

Hom.:

Bravo

AF:

0.000196

ExAC

AF:

0.000134

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

Dec 19, 2022

The c.221G>A (p.G74D) alteration is located in exon 3 (coding exon 3) of the FAM160B2 gene. This alteration results from a G to A substitution at nucleotide position 221, causing the glycine (G) at amino acid position 74 to be replaced by an aspartic acid (D). 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

0.14

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

Eigen

Benign

-0.26

Eigen_PC

Benign

-0.30

FATHMM_MKL

Uncertain

0.85

LIST_S2

Benign

0.74

M_CAP

Benign

0.0026

MetaRNN

Benign

0.045

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

PrimateAI

Uncertain

0.63

PROVEAN

Benign

-0.68

REVEL

Benign

0.075

Sift

Benign

0.12

Sift4G

Uncertain

0.022

Polyphen

0.59

Vest4

0.22

MVP

0.39

MPC

0.068

ClinPred

0.043

GERP RS

2.9

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

2.1

Varity_R

0.072

gMVP

0.22

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