rs1048466

Positions:

• chr12-442384-G-A
• chr12-442384-G-C

Variant summary

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

The NM_032358.4(CCDC77):​c.*464G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.246 in 153,304 control chromosomes in the GnomAD database, including 4,911 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 0.25 (4857 hom., cov: 31)
  • Exomes 𝑓: 0.29 (54 hom.)
• Consequence: CCDC77 NM_032358.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.375

Genes affected

CCDC77 (HGNC:28203): (coiled-coil domain containing 77) Located in centrosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.293 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC77	NM_032358.4	c.*464G>A		3_prime_UTR_variant	13/13	ENST00000239830.9	NP_115734.1
CCDC77	NM_001130146.2	c.*464G>A		3_prime_UTR_variant	12/12		NP_001123618.1
CCDC77	NM_001130147.2	c.*464G>A		3_prime_UTR_variant	12/12		NP_001123619.1
CCDC77	NM_001130148.2	c.*464G>A		3_prime_UTR_variant	11/11		NP_001123620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC77	ENST00000239830.9	c.*464G>A		3_prime_UTR_variant	13/13	2	NM_032358.4	ENSP00000239830	P1
CCDC77	ENST00000412006.6	c.*464G>A		3_prime_UTR_variant	12/12	2		ENSP00000412925
CCDC77	ENST00000422000.5	c.*464G>A		3_prime_UTR_variant	12/12	5		ENSP00000391870
CCDC77	ENST00000537286.1	n.705G>A		non_coding_transcript_exon_variant	2/2	3

Frequencies

GnomAD3 genomes AF: 0.246 AC: 37348 AN: 151860 Hom.: 4854 Cov.: 31

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.195

Gnomad AMR AF: 0.182

Gnomad ASJ AF: 0.193

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.369

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.272

Gnomad OTH AF: 0.210

GnomAD4 exome AF: 0.293 AC: 388 AN: 1324 Hom.: 54 Cov.: 0 AF XY: 0.284 AC XY: 199 AN XY: 700

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.277

Gnomad4 ASJ exome AF: 0.278

Gnomad4 EAS exome AF: 0.429

Gnomad4 SAS exome AF: 0.209

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.304

Gnomad4 OTH exome AF: 0.280

GnomAD4 genome AF: 0.246 AC: 37372 AN: 151980 Hom.: 4857 Cov.: 31 AF XY: 0.249 AC XY: 18526 AN XY: 74266

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.182

Gnomad4 ASJ AF: 0.193

Gnomad4 EAS AF: 0.306

Gnomad4 SAS AF: 0.243

Gnomad4 FIN AF: 0.369

Gnomad4 NFE AF: 0.272

Gnomad4 OTH AF: 0.207

Alfa AF: 0.239 Hom.: 4559

Bravo AF: 0.229

Asia WGS AF: 0.281 AC: 978 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.73
DANN	Benign	0.56

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs1048466; hg19: chr12-551550;