rs9649052

Variant names:

• chr7-135169092-C-A
• rs9649052
• NM_024033.4:c.-138-32G>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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]

ENSG00000272941 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024033.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYREN	NM_024033.4	MANE Select	c.-138-32G>T		intron	N/A	NP_076938.2
	CYREN	NM_001363329.2		c.-138-32G>T		intron	N/A	NP_001350258.1
	CYREN	NM_001363330.2		c.-138-32G>T		intron	N/A	NP_001350259.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYREN	ENST00000393114.8	TSL:1 MANE Select	c.-138-32G>T		intron	N/A	ENSP00000376823.3
	CYREN	ENST00000459937.5	TSL:1	n.45-32G>T		intron	N/A
	CYREN	ENST00000487774.1	TSL:1	n.88-32G>T		intron	N/A

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

African (AFR) AF: 0.417 AC: 5151 AN: 12354

American (AMR) AF: 0.495 AC: 7749 AN: 15654

Ashkenazi Jewish (ASJ) AF: 0.644 AC: 8619 AN: 13386

East Asian (EAS) AF: 0.267 AC: 7542 AN: 28292

South Asian (SAS) AF: 0.649 AC: 28054 AN: 43224

European-Finnish (FIN) AF: 0.492 AC: 14178 AN: 28794

Middle Eastern (MID) AF: 0.580 AC: 1464 AN: 2522

European-Non Finnish (NFE) AF: 0.510 AC: 164767 AN: 323328

Other (OTH) AF: 0.514 AC: 13890 AN: 27036

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

African (AFR) AF: 0.426 AC: 17647 AN: 41454

American (AMR) AF: 0.505 AC: 7712 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.650 AC: 2255 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1248 AN: 5180

South Asian (SAS) AF: 0.648 AC: 3125 AN: 4824

European-Finnish (FIN) AF: 0.481 AC: 5078 AN: 10554

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.510 AC: 34661 AN: 67986

Other (OTH) AF: 0.481 AC: 1014 AN: 2110

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.71
DANN	Benign	0.61
PhyloP100		-0.99
PromoterAI		-0.0048	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9649052; hg19: chr7-134853844;