rs854457

chr3-97879757-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_153605.4(CRYBG3):c.6888+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00129 in 1,587,094 control chromosomes in the GnomAD database, including 20 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0025 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0012 (17 hom.)
• Consequence: CRYBG3 NM_153605.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.353

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.58).
• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0025 (381/152322) while in subpopulation EAS AF= 0.0251 (130/5188). AF 95% confidence interval is 0.0216. There are 3 homozygotes in gnomad4. There are 201 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBG3	NM_153605.4	c.6888+9A>G		intron_variant		ENST00000389622.7
CRYBG3	XM_005247117.5	c.6015+9A>G		intron_variant
CRYBG3	XM_047447439.1	c.6888+9A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG3	ENST00000389622.7	c.6888+9A>G		intron_variant		5	NM_153605.4	P1

Frequencies

GnomAD3 genomes AF: 0.00252 AC: 383 AN: 152204 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00437

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00177

Gnomad ASJ AF: 0.00144

Gnomad EAS AF: 0.0250

Gnomad SAS AF: 0.00393

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.000956

GnomAD3 exomes AF: 0.00302 AC: 716 AN: 237344 Hom.: 7 AF XY: 0.00292 AC XY: 375 AN XY: 128632

Gnomad AFR exome AF: 0.00528

Gnomad AMR exome AF: 0.00127

Gnomad ASJ exome AF: 0.00166

Gnomad EAS exome AF: 0.0288

Gnomad SAS exome AF: 0.00152

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000292

Gnomad OTH exome AF: 0.00140

GnomAD4 exome AF: 0.00116 AC: 1663 AN: 1434772 Hom.: 17 Cov.: 25 AF XY: 0.00117 AC XY: 838 AN XY: 714230

Gnomad4 AFR exome AF: 0.00358

Gnomad4 AMR exome AF: 0.00112

Gnomad4 ASJ exome AF: 0.00144

Gnomad4 EAS exome AF: 0.0207

Gnomad4 SAS exome AF: 0.00148

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000357

Gnomad4 OTH exome AF: 0.00202

GnomAD4 genome AF: 0.00250 AC: 381 AN: 152322 Hom.: 3 Cov.: 32 AF XY: 0.00270 AC XY: 201 AN XY: 74482

Gnomad4 AFR AF: 0.00433

Gnomad4 AMR AF: 0.00176

Gnomad4 ASJ AF: 0.00144

Gnomad4 EAS AF: 0.0251

Gnomad4 SAS AF: 0.00394

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000265

Gnomad4 OTH AF: 0.000473

Alfa AF: 0.00116 Hom.: 0

Bravo AF: 0.00309

Asia WGS AF: 0.0120 AC: 40 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
Cadd	Benign	8.5
Dann	Benign	0.85

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: rs854457; hg19: chr3-97598601;