rs1229

Variant names:

• chr2-65084304-G-A
• rs1229
• NM_015147.3:c.*670G>A

Variant summary

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

The NM_015147.3(CEP68):​c.*670G>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 0.164 in 152,112 control chromosomes in the GnomAD database, including 2,231 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 0.16 (2231 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CEP68 NM_015147.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.96
• Publications: 7 publications found

Genes affected

CEP68 (HGNC:29076): (centrosomal protein 68) Enables protein domain specific binding activity and protein kinase binding activity. Involved in centriole-centriole cohesion and protein localization to organelle. Located in several cellular components, including centriolar satellite; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

RAB1A (HGNC:9758): (RAB1A, member RAS oncogene family) This gene encodes a member of the Ras superfamily of GTPases. Members of the gene family cycle between inactive GDP-bound and active GTP-bound forms. This small GTPase controls vesicle traffic from the endoplasmic reticulum to the Golgi apparatus. Multiple alternatively spliced transcript variants have been identified for this gene which encode different protein isoforms. [provided by RefSeq, Oct 2008]

RAB1A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: G2P

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.228 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP68	NM_015147.3	c.*670G>A		3_prime_UTR_variant	Exon 7 of 7	ENST00000377990.7	NP_055962.2
CEP68	NR_134966.2	n.3006G>A		non_coding_transcript_exon_variant	Exon 6 of 6
CEP68	NM_001319100.2	c.*670G>A		3_prime_UTR_variant	Exon 7 of 7		NP_001306029.1
CEP68	NM_001319101.2	c.*670G>A		3_prime_UTR_variant	Exon 7 of 7		NP_001306030.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP68	ENST00000377990.7	c.*670G>A		3_prime_UTR_variant	Exon 7 of 7	1	NM_015147.3	ENSP00000367229.2

Frequencies

GnomAD3 genomes AF: 0.163 AC: 24843 AN: 151994 Hom.: 2226 Cov.: 32

Gnomad AFR AF: 0.232

Gnomad AMI AF: 0.103

Gnomad AMR AF: 0.126

Gnomad ASJ AF: 0.199

Gnomad EAS AF: 0.102

Gnomad SAS AF: 0.196

Gnomad FIN AF: 0.144

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.134

Gnomad OTH AF: 0.172

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 4 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 2

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.164 AC: 24886 AN: 152112 Hom.: 2231 Cov.: 32 AF XY: 0.163 AC XY: 12154 AN XY: 74384

African (AFR) AF: 0.232 AC: 9623 AN: 41488

American (AMR) AF: 0.126 AC: 1925 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.199 AC: 688 AN: 3466

East Asian (EAS) AF: 0.102 AC: 526 AN: 5178

South Asian (SAS) AF: 0.196 AC: 942 AN: 4818

European-Finnish (FIN) AF: 0.144 AC: 1521 AN: 10588

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.134 AC: 9142 AN: 67986

Other (OTH) AF: 0.176 AC: 370 AN: 2106

Alfa AF: 0.154 Hom.: 666

Bravo AF: 0.164

Asia WGS AF: 0.199 AC: 691 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.021
DANN	Benign	0.57
PhyloP100		-2.0
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: rs1229; hg19: chr2-65311438;