3-97876178-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_153605.4(CRYBG3):c.4984C>A(p.Pro1662Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00311 in 1,231,808 control chromosomes in the GnomAD database, including 80 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 0.015 (50 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (30 hom.)
• Consequence: CRYBG3 NM_153605.4 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.172

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=0.0039158463).
• BP6: Variant 3-97876178-C-A is Benign according to our data. Variant chr3-97876178-C-A is described in ClinVar as [Benign]. Clinvar id is 782430.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.015 (2287/152022) while in subpopulation AFR AF= 0.0518 (2145/41442). AF 95% confidence interval is 0.0499. There are 50 homozygotes in gnomad4. There are 1073 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBG3	NM_153605.4	c.4984C>A	p.Pro1662Thr	missense_variant	4/22	ENST00000389622.7
CRYBG3	XM_005247117.5	c.4111C>A	p.Pro1371Thr	missense_variant	3/21
CRYBG3	XM_047447439.1	c.4984C>A	p.Pro1662Thr	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG3	ENST00000389622.7	c.4984C>A	p.Pro1662Thr	missense_variant	4/22	5	NM_153605.4	P1

Frequencies

GnomAD3 genomes AF: 0.0150 AC: 2278 AN: 151902 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0517

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00676

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.0120

GnomAD4 exome AF: 0.00143 AC: 1542 AN: 1079786 Hom.: 30 Cov.: 35 AF XY: 0.00130 AC XY: 662 AN XY: 509754

Gnomad4 AFR exome AF: 0.0503

Gnomad4 AMR exome AF: 0.00582

Gnomad4 ASJ exome AF: 0.0000695

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000210

Gnomad4 OTH exome AF: 0.00327

GnomAD4 genome AF: 0.0150 AC: 2287 AN: 152022 Hom.: 50 Cov.: 32 AF XY: 0.0144 AC XY: 1073 AN XY: 74308

Gnomad4 AFR AF: 0.0518

Gnomad4 AMR AF: 0.00675

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: 0.0118

Alfa AF: 0.00282 Hom.: 2

Bravo AF: 0.0165

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.000259 AC: 1

Asia WGS AF: 0.00289 AC: 10 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	0.096
BayesDel_addAF	Benign	-0.43	T
BayesDel_noAF	Benign	-0.35
Cadd	Benign	3.4
Dann	Benign	0.58
DEOGEN2	Benign	0.058	T
FATHMM_MKL	Benign	0.14	N
LIST_S2	Benign	0.53	T
MetaRNN	Benign	0.0039	T
Sift4G	Uncertain	0.0070	D
Vest4		0.084
MVP		0.66
GERP RS		1.1
Varity_R		0.040
gMVP		0.0093

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: rs78192445; hg19: chr3-97595022;