Variant 3-97878035-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_153605.4(CRYBG3):c.6841G>A(p.Glu2281Lys) variant causes a missense, splice region change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00564 in 1,597,998 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0047 ( 5 hom., cov: 32)

Exomes 𝑓: 0.0057 ( 30 hom. )

Consequence

CRYBG3
NM_153605.4 missense, splice_region

Scores

Splicing: ADA: 0.0001044

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.65

Variant links:

Genes affected

CRYBG3 (HGNC:34427): (crystallin beta-gamma domain containing 3) Enables protein kinase A binding activity. Predicted to be involved in lens development in camera-type eye and visual perception. Part of protein-containing complex. [provided by Alliance of Genome Resources, Apr 2022]

CRYBG3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0072820187).

BP6

Variant 3-97878035-G-A is Benign according to our data. Variant chr3-97878035-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2653996.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBG3	NM_153605.4 linkuse as main transcript	c.6841G>A	p.Glu2281Lys	missense_variant, splice_region_variant	4/22	ENST00000389622.7	NP_705833.3	Q68DQ2-3
CRYBG3	XM_005247117.5 linkuse as main transcript	c.5968G>A	p.Glu1990Lys	missense_variant, splice_region_variant	3/21		XP_005247174.1
CRYBG3	XM_047447439.1 linkuse as main transcript	c.6841G>A	p.Glu2281Lys	missense_variant, splice_region_variant	4/11		XP_047303395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBG3	ENST00000389622.7 linkuse as main transcript	c.6841G>A	p.Glu2281Lys	missense_variant, splice_region_variant	4/22	5	NM_153605.4	ENSP00000374273.3		Q68DQ2-3

Frequencies

GnomAD3 genomes

AF:

0.00469

AC:

713

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.0373

Gnomad AMR

AF:

0.00262

Gnomad ASJ

AF:

0.000576

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.0101

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00672

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00397

AC:

923

AN:

232646

Hom.:

AF XY:

0.00423

AC XY:

537

AN XY:

126862

show subpopulations

Gnomad AFR exome

AF:

0.000272

Gnomad AMR exome

AF:

0.000810

Gnomad ASJ exome

AF:

0.000450

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00223

Gnomad FIN exome

AF:

0.00923

Gnomad NFE exome

AF:

0.00576

Gnomad OTH exome

AF:

0.00322

GnomAD4 exome

AF:

0.00575

AC:

8306

AN:

1445734

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

4139

AN XY:

719080

show subpopulations

Gnomad4 AFR exome

AF:

0.000807

Gnomad4 AMR exome

AF:

0.00116

Gnomad4 ASJ exome

AF:

0.000398

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00273

Gnomad4 FIN exome

AF:

0.00869

Gnomad4 NFE exome

AF:

0.00661

Gnomad4 OTH exome

AF:

0.00354

GnomAD4 genome

AF:

0.00468

AC:

713

AN:

152264

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

367

AN XY:

74454

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00261

Gnomad4 ASJ

AF:

0.000576

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.0101

Gnomad4 NFE

AF:

0.00672

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00556

Hom.:

Bravo

AF:

0.00405

TwinsUK

AF:

0.00728

AC:

ALSPAC

AF:

0.00778

AC:

ESP6500AA

AF:

0.000835

AC:

ESP6500EA

AF:

0.00457

AC:

ExAC

AF:

0.00360

AC:

434

Asia WGS

AF:

0.00144

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

CRYBG3: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.36

BayesDel_noAF

Benign

-0.28

CADD

Uncertain

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0053

Eigen

Benign

-0.33

Eigen_PC

Benign

-0.23

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.82

M_CAP

Benign

0.0064

MetaRNN

Benign

0.0073

MetaSVM

Benign

-0.94

PrimateAI

Benign

0.42

Sift4G

Uncertain

0.011

Vest4

0.21

MVP

0.31

ClinPred

0.013

GERP RS

3.7

Varity_R

0.043

gMVP

0.38

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00010

dbscSNV1_RF

Benign

0.016

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