ENST00000354451.6:n.266T>C

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 10 publications found

Genes affected

CRYBB2P1 (HGNC:):

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

ACMG classification

Our verdict: Benign. The variant received -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	ENST00000382734.11	n.482T>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

African (AFR) AF: 0.566 AC: 18949 AN: 33454

American (AMR) AF: 0.180 AC: 7997 AN: 44414

Ashkenazi Jewish (ASJ) AF: 0.0788 AC: 2056 AN: 26086

East Asian (EAS) AF: 0.122 AC: 4817 AN: 39640

South Asian (SAS) AF: 0.163 AC: 13992 AN: 85910

European-Finnish (FIN) AF: 0.0727 AC: 3876 AN: 53330

Middle Eastern (MID) AF: 0.123 AC: 706 AN: 5756

European-Non Finnish (NFE) AF: 0.0809 AC: 89865 AN: 1110858

Other (OTH) AF: 0.124 AC: 7488 AN: 60322

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

African (AFR) AF: 0.555 AC: 22934 AN: 41346

American (AMR) AF: 0.175 AC: 2665 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0753 AC: 261 AN: 3468

East Asian (EAS) AF: 0.112 AC: 575 AN: 5156

South Asian (SAS) AF: 0.164 AC: 788 AN: 4810

European-Finnish (FIN) AF: 0.0667 AC: 707 AN: 10594

Middle Eastern (MID) AF: 0.112 AC: 33 AN: 294

European-Non Finnish (NFE) AF: 0.0785 AC: 5334 AN: 67966

Other (OTH) AF: 0.195 AC: 410 AN: 2104

Alfa AF: 0.107 Hom.: 703

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
PhyloP100		4.1
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

Other links and lift over

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