3-97879757-A-G

Variant names:

• chr3-97879757-A-G
• rs854457
• NM_153605.4:c.6888+9A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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 the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_153605.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYBG3	NM_153605.4	MANE Select	c.6888+9A>G		intron	N/A	NP_705833.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CRYBG3	ENST00000389622.7	TSL:5 MANE Select	c.6888+9A>G		intron	N/A	ENSP00000374273.3

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

GnomAD2 exomes AF: 0.00302 AC: 716 AN: 237344 AF XY: 0.00292

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 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

African (AFR) AF: 0.00358 AC: 117 AN: 32674

American (AMR) AF: 0.00112 AC: 48 AN: 42898

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 37 AN: 25672

East Asian (EAS) AF: 0.0207 AC: 813 AN: 39230

South Asian (SAS) AF: 0.00148 AC: 122 AN: 82626

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53192

Middle Eastern (MID) AF: 0.00280 AC: 16 AN: 5708

European-Non Finnish (NFE) AF: 0.000357 AC: 390 AN: 1093282

Other (OTH) AF: 0.00202 AC: 120 AN: 59490

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

African (AFR) AF: 0.00433 AC: 180 AN: 41578

American (AMR) AF: 0.00176 AC: 27 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00144 AC: 5 AN: 3470

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5188

South Asian (SAS) AF: 0.00394 AC: 19 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68014

Other (OTH) AF: 0.000473 AC: 1 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.58
CADD	Benign	8.5
DANN	Benign	0.85
PhyloP100		0.35
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs854457; hg19: chr3-97598601;