22-25457401-T-C

Variant names:

• chr22-25457401-T-C
• rs6423498
• ENST00000354451.6:n.266T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000354451.6(CRYBB2P1):​n.266T>C variant causes a splice region, non coding transcript exon change. The variant allele was found at a frequency of 0.114 in 1,611,690 control chromosomes in the GnomAD database, including 19,883 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 0.22 (7113 hom., cov: 32)
  • Exomes 𝑓: 0.10 (12770 hom.)
• Consequence: CRYBB2P1 ENST00000354451.6 splice_region, non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.12

Genes affected

CRYBB2P1 (HGNC:):

CRYBB2P1 (HGNC:2399): (crystallin beta B2 pseudogene 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.61).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.549 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBB2P1	NR_033733.1	n.589T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 6
CRYBB2P1	NR_033734.1	n.470T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CRYBB2P1	ENST00000354451.6	n.266T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 6	1
CRYBB2P1	ENST00000382734.10	n.477T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 5	1
CRYBB2P1	ENST00000415709.7	n.272T>C		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 3	6

Frequencies

GnomAD3 genomes AF: 0.222 AC: 33625 AN: 151800 Hom.: 7071 Cov.: 32

Gnomad AFR AF: 0.554

Gnomad AMI AF: 0.0307

Gnomad AMR AF: 0.174

Gnomad ASJ AF: 0.0753

Gnomad EAS AF: 0.111

Gnomad SAS AF: 0.164

Gnomad FIN AF: 0.0667

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0785

Gnomad OTH AF: 0.191

GnomAD4 exome AF: 0.103 AC: 149746 AN: 1459770 Hom.: 12770 Cov.: 33 AF XY: 0.103 AC XY: 74620 AN XY: 726036

Gnomad4 AFR exome AF: 0.566

Gnomad4 AMR exome AF: 0.180

Gnomad4 ASJ exome AF: 0.0788

Gnomad4 EAS exome AF: 0.122

Gnomad4 SAS exome AF: 0.163

Gnomad4 FIN exome AF: 0.0727

Gnomad4 NFE exome AF: 0.0809

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.222 AC: 33735 AN: 151920 Hom.: 7113 Cov.: 32 AF XY: 0.220 AC XY: 16332 AN XY: 74306

Gnomad4 AFR AF: 0.555

Gnomad4 AMR AF: 0.175

Gnomad4 ASJ AF: 0.0753

Gnomad4 EAS AF: 0.112

Gnomad4 SAS AF: 0.164

Gnomad4 FIN AF: 0.0667

Gnomad4 NFE AF: 0.0785

Gnomad4 OTH AF: 0.195

Alfa AF: 0.0443 Hom.: 39

Bravo AF: 0.246

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	16
DANN	Benign	0.72
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs6423498; hg19: chr22-25853368; COSMIC: COSV63115362;