rs62001006

Variant names:

• chr5-624472-C-T
• rs62001006
• NM_018140.4:c.405C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_018140.4(CEP72):​c.405C>T​(p.Asp135Asp) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.003 in 1,613,180 control chromosomes in the GnomAD database, including 39 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0054 (9 hom., cov: 32)
  • Exomes 𝑓: 0.0027 (30 hom.)
• Consequence: CEP72 NM_018140.4 splice_region, synonymous
• Scores: Splicing: ADA: 0.000009227
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.660
• Publications: 6 publications found

Genes affected

CEP72 (HGNC:25547): (centrosomal protein 72) The product of this gene is a member of the leucine-rich-repeat (LRR) superfamily of proteins. The protein is localized to the centrosome, a non-membraneous organelle that functions as the major microtubule-organizing center in animal cells. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 5-624472-C-T is Benign according to our data. Variant chr5-624472-C-T is described in ClinVar as Benign. ClinVar VariationId is 775221.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=0.66 with no splicing effect.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00542 (826/152334) while in subpopulation AMR AF = 0.0171 (262/15306). AF 95% confidence interval is 0.0154. There are 9 homozygotes in GnomAd4. There are 398 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 9 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018140.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP72	NM_018140.4	MANE Select	c.405C>T	p.Asp135Asp	splice_region synonymous	Exon 4 of 12	NP_060610.2	Q9P209-1
	CEP72	NR_164122.1		n.585C>T		splice_region non_coding_transcript_exon	Exon 4 of 16

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP72	ENST00000264935.6	TSL:1 MANE Select	c.405C>T	p.Asp135Asp	splice_region synonymous	Exon 4 of 12	ENSP00000264935.5	Q9P209-1
	CEP72	ENST00000856935.1		c.405C>T	p.Asp135Asp	splice_region synonymous	Exon 4 of 13	ENSP00000526994.1
	CEP72	ENST00000919286.1		c.405C>T	p.Asp135Asp	splice_region synonymous	Exon 4 of 12	ENSP00000589345.1

Frequencies

GnomAD3 genomes AF: 0.00543 AC: 826 AN: 152216 Hom.: 9 Cov.: 32

Gnomad AFR AF: 0.00772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0171

Gnomad ASJ AF: 0.0158

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.00220

Gnomad OTH AF: 0.0129

GnomAD2 exomes AF: 0.00430 AC: 1082 AN: 251406 AF XY: 0.00417

Gnomad AFR exome AF: 0.00714

Gnomad AMR exome AF: 0.0100

Gnomad ASJ exome AF: 0.0225

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.000508

Gnomad NFE exome AF: 0.00274

Gnomad OTH exome AF: 0.00782

GnomAD4 exome AF: 0.00274 AC: 4009 AN: 1460846 Hom.: 30 Cov.: 30 AF XY: 0.00277 AC XY: 2014 AN XY: 726822

African (AFR) AF: 0.00688 AC: 230 AN: 33454

American (AMR) AF: 0.0109 AC: 489 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0191 AC: 498 AN: 26124

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39688

South Asian (SAS) AF: 0.000545 AC: 47 AN: 86240

European-Finnish (FIN) AF: 0.000468 AC: 25 AN: 53418

Middle Eastern (MID) AF: 0.0277 AC: 160 AN: 5768

European-Non Finnish (NFE) AF: 0.00195 AC: 2170 AN: 1111066

Other (OTH) AF: 0.00644 AC: 389 AN: 60364

GnomAD4 genome AF: 0.00542 AC: 826 AN: 152334 Hom.: 9 Cov.: 32 AF XY: 0.00534 AC XY: 398 AN XY: 74494

African (AFR) AF: 0.00770 AC: 320 AN: 41576

American (AMR) AF: 0.0171 AC: 262 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.0158 AC: 55 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.000415 AC: 2 AN: 4822

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10618

Middle Eastern (MID) AF: 0.0306 AC: 9 AN: 294

European-Non Finnish (NFE) AF: 0.00220 AC: 150 AN: 68036

Other (OTH) AF: 0.0128 AC: 27 AN: 2114

Alfa AF: 0.00412 Hom.: 8

Bravo AF: 0.00727

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00414

EpiControl AF: 0.00397

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	1.5
DANN	Benign	0.48
PhyloP100		0.66
Mutation Taster		=78/22	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000092
dbscSNV1_RF	Benign	0.0080
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: rs62001006; hg19: chr5-624587;