Variant 3-97875489-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_153605.4(CRYBG3):c.4295C>T(p.Ser1432Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,298,622 control chromosomes in the GnomAD database, including 42 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 0.012 ( 23 hom., cov: 32)

Exomes 𝑓: 0.0011 ( 19 hom. )

Consequence

CRYBG3
NM_153605.4 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.172

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=0.0041623414).

BP6

Variant 3-97875489-C-T is Benign according to our data. Variant chr3-97875489-C-T is described in ClinVar as [Benign]. Clinvar id is 782429.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1777/152216) while in subpopulation AFR AF= 0.04 (1662/41536). AF 95% confidence interval is 0.0384. There are 23 homozygotes in gnomad4. There are 825 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CRYBG3	NM_153605.4 link	c.4295C>T	p.Ser1432Leu	missense_variant	4/22	ENST00000389622.7	NP_705833.3	Q68DQ2-3
CRYBG3	XM_005247117.5 link	c.3422C>T	p.Ser1141Leu	missense_variant	3/21		XP_005247174.1
CRYBG3	XM_047447439.1 link	c.4295C>T	p.Ser1432Leu	missense_variant	4/11		XP_047303395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CRYBG3	ENST00000389622.7 link	c.4295C>T	p.Ser1432Leu	missense_variant	4/22	5	NM_153605.4	ENSP00000374273.3		Q68DQ2-3

Frequencies

GnomAD3 genomes

AF:

0.0116

AC:

1771

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0400

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00544

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00637

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00907

GnomAD4 exome

AF:

0.00114

AC:

1311

AN:

1146406

Hom.:

Cov.:

AF XY:

0.00105

AC XY:

570

AN XY:

544836

show subpopulations

Gnomad4 AFR exome

AF:

0.0400

Gnomad4 AMR exome

AF:

0.00428

Gnomad4 ASJ exome

AF:

0.0000625

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000334

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000201

Gnomad4 OTH exome

AF:

0.00237

GnomAD4 genome

AF:

0.0117

AC:

1777

AN:

152216

Hom.:

Cov.:

AF XY:

0.0111

AC XY:

825

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.0400

Gnomad4 AMR

AF:

0.00543

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000162

Gnomad4 OTH

AF:

0.00898

Alfa

AF:

0.00964

Hom.:

Bravo

AF:

0.0129

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.000259

AC:

Asia WGS

AF:

0.00202

AC:

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

0.098

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.48

CADD

Benign

9.7

DANN

Benign

0.66

DEOGEN2

Benign

0.0055

FATHMM_MKL

Benign

0.045

LIST_S2

Benign

0.61

MetaRNN

Benign

0.0042

Sift4G

Uncertain

0.053

Vest4

0.11

MVP

0.68

GERP RS

3.4

Varity_R

0.12

gMVP

0.019

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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