rs2278664

Positions:

• chr18-24139363-C-T

Variant summary

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

The NM_153769.3(CABYR):​c.-25+245C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,056 control chromosomes in the GnomAD database, including 20,421 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 0.47 (20397 hom., cov: 31)
  • Exomes 𝑓: 0.65 (24 hom.)
• Consequence: CABYR NM_153769.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.214

Genes affected

CABYR (HGNC:15569): (calcium binding tyrosine phosphorylation regulated) To reach fertilization competence, spermatozoa undergo a series of morphological and molecular maturational processes, termed capacitation, involving protein tyrosine phosphorylation and increased intracellular calcium. The protein encoded by this gene localizes to the principal piece of the sperm flagellum in association with the fibrous sheath and exhibits calcium-binding when phosphorylated during capacitation. A pseudogene on chromosome 3 has been identified for this gene. Alternatively spliced transcript variants encoding distinct protein isoforms have been found for this gene. [provided by RefSeq, Jul 2013]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.638 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CABYR	NM_153769.3	c.-25+245C>T		intron_variant		ENST00000399496.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CABYR	ENST00000399496.8	c.-25+245C>T		intron_variant		1	NM_153769.3	P1

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71690 AN: 151834 Hom.: 20397 Cov.: 31

Gnomad AFR AF: 0.146

Gnomad AMI AF: 0.515

Gnomad AMR AF: 0.512

Gnomad ASJ AF: 0.610

Gnomad EAS AF: 0.397

Gnomad SAS AF: 0.453

Gnomad FIN AF: 0.580

Gnomad MID AF: 0.491

Gnomad NFE AF: 0.643

Gnomad OTH AF: 0.521

GnomAD4 exome AF: 0.647 AC: 66 AN: 102 Hom.: 24 AF XY: 0.654 AC XY: 51 AN XY: 78

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 1.00

Gnomad4 EAS exome AF: 0.250

Gnomad4 FIN exome AF: 0.400

Gnomad4 NFE exome AF: 0.711

Gnomad4 OTH exome AF: 0.625

GnomAD4 genome AF: 0.472 AC: 71693 AN: 151954 Hom.: 20397 Cov.: 31 AF XY: 0.470 AC XY: 34858 AN XY: 74220

Gnomad4 AFR AF: 0.146

Gnomad4 AMR AF: 0.511

Gnomad4 ASJ AF: 0.610

Gnomad4 EAS AF: 0.396

Gnomad4 SAS AF: 0.454

Gnomad4 FIN AF: 0.580

Gnomad4 NFE AF: 0.643

Gnomad4 OTH AF: 0.523

Alfa AF: 0.610 Hom.: 38255

Bravo AF: 0.449

Asia WGS AF: 0.436 AC: 1514 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	7.1
DANN	Benign	0.78

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2278664; hg19: chr18-21719327;