22-41822852-A-G

Variant names:

• chr22-41822852-A-G
• rs7364180
• NM_024821.5:c.565-2846A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024821.5(CCDC134):​c.565-2846A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 152,072 control chromosomes in the GnomAD database, including 12,755 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 0.38 (12755 hom., cov: 32)
• Consequence: CCDC134 NM_024821.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.242
• Publications: 28 publications found

Genes affected

CCDC134 (HGNC:26185): (coiled-coil domain containing 134) Predicted to act upstream of or within angiogenesis and animal organ development. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC134 Gene-Disease associations (from GenCC):

• osteogenesis imperfecta

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• osteogenesis imperfecta, IIA 22

  Inheritance: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.571 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024821.5. 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
	CCDC134	NM_024821.5	MANE Select	c.565-2846A>G		intron	N/A	NP_079097.1
	CCDC134	NM_001382346.1		c.565-2846A>G		intron	N/A	NP_001369275.1
	CCDC134	NM_001304797.2		c.226-2846A>G		intron	N/A	NP_001291726.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC134	ENST00000255784.6	TSL:1 MANE Select	c.565-2846A>G		intron	N/A	ENSP00000255784.5
	CCDC134	ENST00000402061.8	TSL:2	c.226-2846A>G		intron	N/A	ENSP00000385803.3

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57653 AN: 151954 Hom.: 12697 Cov.: 32

Gnomad AFR AF: 0.576

Gnomad AMI AF: 0.325

Gnomad AMR AF: 0.515

Gnomad ASJ AF: 0.422

Gnomad EAS AF: 0.249

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.226

Gnomad MID AF: 0.373

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.356

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.380 AC: 57776 AN: 152072 Hom.: 12755 Cov.: 32 AF XY: 0.380 AC XY: 28275 AN XY: 74348

African (AFR) AF: 0.578 AC: 23940 AN: 41450

American (AMR) AF: 0.516 AC: 7885 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.422 AC: 1466 AN: 3470

East Asian (EAS) AF: 0.248 AC: 1284 AN: 5168

South Asian (SAS) AF: 0.363 AC: 1748 AN: 4820

European-Finnish (FIN) AF: 0.226 AC: 2394 AN: 10606

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.264 AC: 17911 AN: 67968

Other (OTH) AF: 0.352 AC: 741 AN: 2108

Alfa AF: 0.320 Hom.: 24044

Bravo AF: 0.414

Asia WGS AF: 0.331 AC: 1149 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.0
DANN	Benign	0.89
PhyloP100		0.24
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: rs7364180; hg19: chr22-42218856;