rs9649052

Positions:

• chr7-135169092-C-A

Variant summary

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

The NM_024033.4(CYREN):​c.-138-32G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 646,646 control chromosomes in the GnomAD database, including 84,305 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 0.48 (18064 hom., cov: 32)
  • Exomes 𝑓: 0.51 (66241 hom.)
• Consequence: CYREN NM_024033.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.993

Genes affected

CYREN (HGNC:22432): (cell cycle regulator of NHEJ) Involved in double-strand break repair via nonhomologous end joining and negative regulation of double-strand break repair via nonhomologous end joining. Located in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

CYREN (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.629 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYREN	NM_024033.4	c.-138-32G>T		intron_variant		ENST00000393114.8	NP_076938.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYREN	ENST00000393114.8	c.-138-32G>T		intron_variant		1	NM_024033.4	ENSP00000376823.3

Frequencies

GnomAD3 genomes AF: 0.483 AC: 73416 AN: 151938 Hom.: 18037 Cov.: 32

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.635

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.650

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.647

Gnomad FIN AF: 0.481

Gnomad MID AF: 0.620

Gnomad NFE AF: 0.510

Gnomad OTH AF: 0.478

GnomAD4 exome AF: 0.508 AC: 251414 AN: 494590 Hom.: 66241 Cov.: 6 AF XY: 0.515 AC XY: 132474 AN XY: 257344

Gnomad4 AFR exome AF: 0.417

Gnomad4 AMR exome AF: 0.495

Gnomad4 ASJ exome AF: 0.644

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.649

Gnomad4 FIN exome AF: 0.492

Gnomad4 NFE exome AF: 0.510

Gnomad4 OTH exome AF: 0.514

GnomAD4 genome AF: 0.483 AC: 73498 AN: 152056 Hom.: 18064 Cov.: 32 AF XY: 0.483 AC XY: 35896 AN XY: 74306

Gnomad4 AFR AF: 0.426

Gnomad4 AMR AF: 0.505

Gnomad4 ASJ AF: 0.650

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.648

Gnomad4 FIN AF: 0.481

Gnomad4 NFE AF: 0.510

Gnomad4 OTH AF: 0.481

Alfa AF: 0.499 Hom.: 5390

Bravo AF: 0.478

Asia WGS AF: 0.482 AC: 1674 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.71
DANN	Benign	0.61

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

Publications

LitVar

Other links and lift over

dbSNP: rs9649052; hg19: chr7-134853844;