rs9320660

Variant names:

• chr6-118635664-A-T
• rs9320660
• NM_001042475.3:c.74-3053T>A

Variant summary

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

The NM_001042475.3(CEP85L):​c.74-3053T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,206 control chromosomes in the GnomAD database, including 2,163 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 (2163 hom., cov: 33)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.289
• Publications: 6 publications found

Genes affected

CEP85L (HGNC:21638): (centrosomal protein 85 like) The protein encoded by this gene was identified as a breast cancer antigen. Nothing more is known of its function at this time. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2010]

CEP85L Gene-Disease associations (from GenCC):

• lissencephaly 10

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• lissencephaly due to LIS1 mutation

  Inheritance: AD Classification: STRONG Submitted by: Illumina

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.186 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.74-3053T>A		intron_variant	Intron 1 of 12	ENST00000368491.8	NP_001035940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8	c.74-3053T>A		intron_variant	Intron 1 of 12	1	NM_001042475.3	ENSP00000357477.3

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24888 AN: 152088 Hom.: 2156 Cov.: 33

Gnomad AFR AF: 0.126

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.149

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0511

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.178

Gnomad NFE AF: 0.189

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.164 AC: 24918 AN: 152206 Hom.: 2163 Cov.: 33 AF XY: 0.164 AC XY: 12231 AN XY: 74418

African (AFR) AF: 0.127 AC: 5263 AN: 41540

American (AMR) AF: 0.149 AC: 2280 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 766 AN: 3470

East Asian (EAS) AF: 0.0510 AC: 265 AN: 5192

South Asian (SAS) AF: 0.141 AC: 678 AN: 4818

European-Finnish (FIN) AF: 0.211 AC: 2231 AN: 10596

Middle Eastern (MID) AF: 0.161 AC: 47 AN: 292

European-Non Finnish (NFE) AF: 0.189 AC: 12820 AN: 67998

Other (OTH) AF: 0.169 AC: 356 AN: 2112

Alfa AF: 0.188 Hom.: 333

Bravo AF: 0.157

Asia WGS AF: 0.115 AC: 401 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	3.0
DANN	Benign	0.51
PhyloP100		-0.29
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: rs9320660; hg19: chr6-118956827;