3-97875417-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.635

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
CRYBG3	NM_153605.4	c.4223G>A	p.Gly1408Glu	missense_variant	4/22	ENST00000389622.7
CRYBG3	XM_005247117.5	c.3350G>A	p.Gly1117Glu	missense_variant	3/21
CRYBG3	XM_047447439.1	c.4223G>A	p.Gly1408Glu	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG3	ENST00000389622.7	c.4223G>A	p.Gly1408Glu	missense_variant	4/22	5	NM_153605.4	P1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69665 AN: 151906 Hom.: 16800 Cov.: 32

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.: 35 AF XY: 0.506 AC XY: 306769 AN XY: 605872

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.: 32 AF XY: 0.465 AC XY: 34538 AN XY: 74302

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 23, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.25
Cadd	Benign	12
Dann	Benign	0.60
DEOGEN2	Benign	0.0072	T
FATHMM_MKL	Benign	0.70	D
LIST_S2	Benign	0.48	T
MetaRNN	Benign	0.0050	T
Sift4G	Benign	0.11	T
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

Other links and lift over

dbSNP: rs6782766; hg19: chr3-97594261; COSMIC: COSV51710280; COSMIC: COSV51710280;