3-97875489-C-T

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.4295C>T(p.Ser1432Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00238 in 1,298,622 control chromosomes in the GnomAD database, including 42 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 0.012 (23 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (19 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=0.0041623414).
• BP6: Variant 3-97875489-C-T is Benign according to our data. Variant chr3-97875489-C-T is described in ClinVar as [Benign]. Clinvar id is 782429.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0117 (1777/152216) while in subpopulation AFR AF= 0.04 (1662/41536). AF 95% confidence interval is 0.0384. There are 23 homozygotes in gnomad4. There are 825 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 23 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CRYBG3	NM_153605.4	c.4295C>T	p.Ser1432Leu	missense_variant	4/22	ENST00000389622.7
CRYBG3	XM_005247117.5	c.3422C>T	p.Ser1141Leu	missense_variant	3/21
CRYBG3	XM_047447439.1	c.4295C>T	p.Ser1432Leu	missense_variant	4/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CRYBG3	ENST00000389622.7	c.4295C>T	p.Ser1432Leu	missense_variant	4/22	5	NM_153605.4	P1

Frequencies

GnomAD3 genomes AF: 0.0116 AC: 1771 AN: 152100 Hom.: 23 Cov.: 32

Gnomad AFR AF: 0.0400

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00544

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00907

GnomAD4 exome AF: 0.00114 AC: 1311 AN: 1146406 Hom.: 19 Cov.: 34 AF XY: 0.00105 AC XY: 570 AN XY: 544836

Gnomad4 AFR exome AF: 0.0400

Gnomad4 AMR exome AF: 0.00428

Gnomad4 ASJ exome AF: 0.0000625

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000334

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000201

Gnomad4 OTH exome AF: 0.00237

GnomAD4 genome AF: 0.0117 AC: 1777 AN: 152216 Hom.: 23 Cov.: 32 AF XY: 0.0111 AC XY: 825 AN XY: 74420

Gnomad4 AFR AF: 0.0400

Gnomad4 AMR AF: 0.00543

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: 0.00898

Alfa AF: 0.00964 Hom.: 4

Bravo AF: 0.0129

TwinsUK AF: 0.00 AC: 0

ALSPAC AF: 0.000259 AC: 1

Asia WGS AF: 0.00202 AC: 7 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	0.098
BayesDel_addAF	Benign	-0.51	T
BayesDel_noAF	Benign	-0.48
Cadd	Benign	9.7
Dann	Benign	0.66
DEOGEN2	Benign	0.0055	T
FATHMM_MKL	Benign	0.045	N
LIST_S2	Benign	0.61	T
MetaRNN	Benign	0.0042	T
Sift4G	Uncertain	0.053	T
Vest4		0.11
MVP		0.68
GERP RS		3.4
Varity_R		0.12
gMVP		0.019

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs115192461; hg19: chr3-97594333;