rs12637414

Variant names:

• chr3-97887828-A-G
• rs12637414
• NM_153605.4:c.7290-513A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_153605.4(CRYBG3):​c.7290-513A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0937 in 152,222 control chromosomes in the GnomAD database, including 860 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 0.094 (860 hom., cov: 32)
• Consequence: CRYBG3 NM_153605.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.247
• Publications: 6 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=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.131 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBG3	NM_153605.4	c.7290-513A>G		intron_variant	Intron 8 of 21	ENST00000389622.7	NP_705833.3
CRYBG3	XM_005247117.5	c.6417-513A>G		intron_variant	Intron 7 of 20		XP_005247174.1
CRYBG3	XM_047447439.1	c.7290-513A>G		intron_variant	Intron 8 of 10		XP_047303395.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBG3	ENST00000389622.7	c.7290-513A>G		intron_variant	Intron 8 of 21	5	NM_153605.4	ENSP00000374273.3

Frequencies

GnomAD3 genomes AF: 0.0938 AC: 14269 AN: 152104 Hom.: 862 Cov.: 32

Gnomad AFR AF: 0.0246

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0877

Gnomad ASJ AF: 0.110

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.128

Gnomad FIN AF: 0.0933

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.0947

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0937 AC: 14261 AN: 152222 Hom.: 860 Cov.: 32 AF XY: 0.0925 AC XY: 6883 AN XY: 74426

African (AFR) AF: 0.0245 AC: 1018 AN: 41558

American (AMR) AF: 0.0874 AC: 1336 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.110 AC: 382 AN: 3472

East Asian (EAS) AF: 0.113 AC: 585 AN: 5166

South Asian (SAS) AF: 0.128 AC: 618 AN: 4822

European-Finnish (FIN) AF: 0.0933 AC: 989 AN: 10604

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.133 AC: 9076 AN: 68000

Other (OTH) AF: 0.0942 AC: 199 AN: 2112

Alfa AF: 0.118 Hom.: 2136

Bravo AF: 0.0891

Asia WGS AF: 0.111 AC: 383 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	16
DANN	Benign	0.88
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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: rs12637414; hg19: chr3-97606672;