3-97876441-C-T

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_153605.4(CRYBG3):c.5247C>T(p.Asp1749=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00061 in 1,231,966 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00066 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00060 (2 hom.)
• Consequence: CRYBG3 NM_153605.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.784

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 3-97876441-C-T is Benign according to our data. Variant chr3-97876441-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2653995.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.784 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBG3	NM_153605.4	c.5247C>T	p.Asp1749=	synonymous_variant	4/22	ENST00000389622.7
CRYBG3	XM_005247117.5	c.4374C>T	p.Asp1458=	synonymous_variant	3/21
CRYBG3	XM_047447439.1	c.5247C>T	p.Asp1749=	synonymous_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG3	ENST00000389622.7	c.5247C>T	p.Asp1749=	synonymous_variant	4/22	5	NM_153605.4	P1

Frequencies

GnomAD3 genomes AF: 0.000664 AC: 101 AN: 152014 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000131

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.000623

Gnomad FIN AF: 0.0000945

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000529

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000603 AC: 651 AN: 1079834 Hom.: 2 Cov.: 35 AF XY: 0.000620 AC XY: 316 AN XY: 509770

Gnomad4 AFR exome AF: 0.00152

Gnomad4 AMR exome AF: 0.000475

Gnomad4 ASJ exome AF: 0.0000695

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000821

Gnomad4 FIN exome AF: 0.000232

Gnomad4 NFE exome AF: 0.000617

Gnomad4 OTH exome AF: 0.000481

GnomAD4 genome AF: 0.000664 AC: 101 AN: 152132 Hom.: 0 Cov.: 32 AF XY: 0.000659 AC XY: 49 AN XY: 74372

Gnomad4 AFR AF: 0.00140

Gnomad4 AMR AF: 0.000131

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.000624

Gnomad4 FIN AF: 0.0000945

Gnomad4 NFE AF: 0.000529

Gnomad4 OTH AF: 0.00

Alfa AF: 0.000529 Hom.: 0

Bravo AF: 0.000676

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Oct 01, 2022

CRYBG3: BP4, BP7 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.0
Dann	Benign	0.60

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: rs146175676; hg19: chr3-97595285; COSMIC: COSV51713326; COSMIC: COSV51713326;