22-25457401-T-G

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000354451.6(CRYBB2P1):​n.266T>G variant causes a splice region, non coding transcript exon change. The variant allele was found at a frequency of 0.0000219 in 1,459,928 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 0.000022 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CRYBB2P1	NR_033733.1	n.589T>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 4 of 6
CRYBB2P1	NR_033734.1	n.470T>G		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>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 6	1
CRYBB2P1	ENST00000382734.10	n.477T>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 3 of 5	1
CRYBB2P1	ENST00000415709.7	n.272T>G		splice_region_variant, non_coding_transcript_exon_variant	Exon 2 of 3	6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.0000219 AC: 32 AN: 1459928 Hom.: 0 Cov.: 33 AF XY: 0.0000220 AC XY: 16 AN XY: 726134

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000113

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000225

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	15
DANN	Benign	0.73

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;