Variant 3-97875417-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_153605.4(CRYBG3):c.4223G>A(p.Gly1408Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 1,406,160 control chromosomes in the GnomAD database, including 179,984 homozygotes. In-silico tool predicts a benign outcome for this variant. 8/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16807 hom., cov: 32)

Exomes 𝑓: 0.51 ( 163177 hom. )

Consequence

CRYBG3
NM_153605.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.635

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0049929917).

BP6

Variant 3-97875417-G-A is Benign according to our data. Variant chr3-97875417-G-A is described in ClinVar as [Benign]. Clinvar id is 769275.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.652 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBG3	NM_153605.4 linkuse as main transcript	c.4223G>A	p.Gly1408Glu	missense_variant	4/22	ENST00000389622.7	NP_705833.3	Q68DQ2-3
CRYBG3	XM_005247117.5 linkuse as main transcript	c.3350G>A	p.Gly1117Glu	missense_variant	3/21		XP_005247174.1
CRYBG3	XM_047447439.1 linkuse as main transcript	c.4223G>A	p.Gly1408Glu	missense_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.4223G>A	p.Gly1408Glu	missense_variant	4/22	5	NM_153605.4	ENSP00000374273.3		Q68DQ2-3

Frequencies

GnomAD3 genomes

AF:

0.459

AC:

69665

AN:

151906

Hom.:

16800

Cov.:

show subpopulations

Gnomad AFR

AF:

0.292

Gnomad AMI

AF:

0.665

Gnomad AMR

AF:

0.524

Gnomad ASJ

AF:

0.520

Gnomad EAS

AF:

0.670

Gnomad SAS

AF:

0.501

Gnomad FIN

AF:

0.553

Gnomad MID

AF:

0.411

Gnomad NFE

AF:

0.506

Gnomad OTH

AF:

0.460

GnomAD4 exome

AF:

0.507

AC:

635733

AN:

1254136

Hom.:

163177

Cov.:

AF XY:

0.506

AC XY:

306769

AN XY:

605872

show subpopulations

Gnomad4 AFR exome

AF:

0.284

Gnomad4 AMR exome

AF:

0.518

Gnomad4 ASJ exome

AF:

0.536

Gnomad4 EAS exome

AF:

0.704

Gnomad4 SAS exome

AF:

0.492

Gnomad4 FIN exome

AF:

0.544

Gnomad4 NFE exome

AF:

0.506

Gnomad4 OTH exome

AF:

0.496

GnomAD4 genome

AF:

0.458

AC:

69696

AN:

152024

Hom.:

16807

Cov.:

AF XY:

0.465

AC XY:

34538

AN XY:

74302

show subpopulations

Gnomad4 AFR

AF:

0.292

Gnomad4 AMR

AF:

0.525

Gnomad4 ASJ

AF:

0.520

Gnomad4 EAS

AF:

0.671

Gnomad4 SAS

AF:

0.499

Gnomad4 FIN

AF:

0.553

Gnomad4 NFE

AF:

0.506

Gnomad4 OTH

AF:

0.464

Alfa

AF:

0.488

Hom.:

5647

Bravo

AF:

0.449

TwinsUK

AF:

0.510

AC:

1892

ALSPAC

AF:

0.513

AC:

1979

Asia WGS

AF:

0.600

AC:

2082

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.25

CADD

Benign

DANN

Benign

0.60

DEOGEN2

Benign

0.0072

FATHMM_MKL

Benign

0.70

LIST_S2

Benign

0.48

MetaRNN

Benign

0.0050

Sift4G

Benign

0.11

Vest4

0.13

MVP

0.68

GERP RS

5.4

Varity_R

0.13

gMVP

0.055

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