3-97876535-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.5341G>A(p.Val1781Met) 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 1,231,604 control chromosomes in the GnomAD database, including 157,675 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 (16818 hom., cov: 31)
  • Exomes 𝑓: 0.51 (140857 hom.)
• Consequence: CRYBG3 NM_153605.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -3.52

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=0.004988253).
• BP6: Variant 3-97876535-G-A is Benign according to our data. Variant chr3-97876535-G-A is described in ClinVar as [Benign]. Clinvar id is 769276.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.648 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBG3	NM_153605.4	c.5341G>A	p.Val1781Met	missense_variant	4/22	ENST00000389622.7
CRYBG3	XM_005247117.5	c.4468G>A	p.Val1490Met	missense_variant	3/21
CRYBG3	XM_047447439.1	c.5341G>A	p.Val1781Met	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG3	ENST00000389622.7	c.5341G>A	p.Val1781Met	missense_variant	4/22	5	NM_153605.4	P1

Frequencies

GnomAD3 genomes AF: 0.459 AC: 69705 AN: 151838 Hom.: 16810 Cov.: 31

Gnomad AFR AF: 0.295

Gnomad AMI AF: 0.662

Gnomad AMR AF: 0.524

Gnomad ASJ AF: 0.520

Gnomad EAS AF: 0.666

Gnomad SAS AF: 0.501

Gnomad FIN AF: 0.551

Gnomad MID AF: 0.415

Gnomad NFE AF: 0.506

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.508 AC: 548554 AN: 1079648 Hom.: 140857 Cov.: 39 AF XY: 0.508 AC XY: 258962 AN XY: 509718

Gnomad4 AFR exome AF: 0.288

Gnomad4 AMR exome AF: 0.509

Gnomad4 ASJ exome AF: 0.538

Gnomad4 EAS exome AF: 0.711

Gnomad4 SAS exome AF: 0.505

Gnomad4 FIN exome AF: 0.543

Gnomad4 NFE exome AF: 0.507

Gnomad4 OTH exome AF: 0.497

GnomAD4 genome AF: 0.459 AC: 69744 AN: 151956 Hom.: 16818 Cov.: 31 AF XY: 0.465 AC XY: 34535 AN XY: 74244

Gnomad4 AFR AF: 0.295

Gnomad4 AMR AF: 0.524

Gnomad4 ASJ AF: 0.520

Gnomad4 EAS AF: 0.666

Gnomad4 SAS AF: 0.500

Gnomad4 FIN AF: 0.551

Gnomad4 NFE AF: 0.506

Gnomad4 OTH AF: 0.468

Alfa AF: 0.498 Hom.: 38801

Bravo AF: 0.450

TwinsUK AF: 0.510 AC: 1892

ALSPAC AF: 0.514 AC: 1980

Asia WGS AF: 0.603 AC: 2095 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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.094
BayesDel_addAF	Benign	-0.67	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.0020
Dann	Benign	0.61
DEOGEN2	Benign	0.00094	T
FATHMM_MKL	Benign	0.0033	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.0050	T
Sift4G	Benign	0.068	T
Vest4		0.058
MVP		0.22
GERP RS		-8.4
Varity_R		0.017
gMVP		0.026

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: rs6786354; hg19: chr3-97595379; COSMIC: COSV51713746; COSMIC: COSV51713746;