rs248450

Positions:

• chr5-151197206-G-A
• chr5-151197206-G-C

Variant summary

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

The ENST00000355417.7(CCDC69):​c.319+1791C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.599 in 152,074 control chromosomes in the GnomAD database, including 28,142 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 0.60 (28142 hom., cov: 32)
• Consequence: CCDC69 ENST00000355417.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.376

Genes affected

CCDC69 (HGNC:24487): (coiled-coil domain containing 69) Predicted to enable microtubule binding activity. Involved in spindle midzone assembly. Located in spindle midzone. [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=-0.86).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.671 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC69	NM_015621.3	c.319+1791C>T		intron_variant		ENST00000355417.7	NP_056436.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC69	ENST00000355417.7	c.319+1791C>T		intron_variant		1	NM_015621.3	ENSP00000347586	P1
CCDC69	ENST00000518189.5	c.273+1791C>T		intron_variant, NMD_transcript_variant		1		ENSP00000430549
CCDC69	ENST00000521308.5	n.366+1791C>T		intron_variant, non_coding_transcript_variant		1
CCDC69	ENST00000522964.1	c.183+4376C>T		intron_variant, NMD_transcript_variant		5		ENSP00000428588

Frequencies

GnomAD3 genomes AF: 0.599 AC: 91052 AN: 151956 Hom.: 28109 Cov.: 32

Gnomad AFR AF: 0.484

Gnomad AMI AF: 0.670

Gnomad AMR AF: 0.682

Gnomad ASJ AF: 0.642

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.484

Gnomad FIN AF: 0.677

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.640

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

GnomAD4 genome AF: 0.599 AC: 91127 AN: 152074 Hom.: 28142 Cov.: 32 AF XY: 0.598 AC XY: 44439 AN XY: 74320

Gnomad4 AFR AF: 0.484

Gnomad4 AMR AF: 0.682

Gnomad4 ASJ AF: 0.642

Gnomad4 EAS AF: 0.280

Gnomad4 SAS AF: 0.484

Gnomad4 FIN AF: 0.677

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.643

Alfa AF: 0.651 Hom.: 65560

Bravo AF: 0.594

Asia WGS AF: 0.417 AC: 1451 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.1
DANN	Benign	0.68

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: rs248450; hg19: chr5-150576767;