6-118569065-G-C

Variant names:

• chr6-118569065-G-C
• rs35407905
• NM_001042475.3:c.233-2749C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_Strong BS2_Supporting

The NM_001042475.3(CEP85L):​c.233-2749C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000725 in 151,780 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 0.000072 (0 hom., cov: 31)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0340
• Publications: 1 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

ENSG00000286339 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS2: High AC in GnomAd4 at 11 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001042475.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	NM_001042475.3	MANE Select	c.233-2749C>G		intron	N/A	NP_001035940.1
	CEP85L	NM_001178035.2		c.242-2749C>G		intron	N/A	NP_001171506.1
	CEP85L	NM_206921.3		c.233-2749C>G		intron	N/A	NP_996804.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	ENST00000368491.8	TSL:1 MANE Select	c.233-2749C>G		intron	N/A	ENSP00000357477.3
	CEP85L	ENST00000434604.5	TSL:1	c.242-2749C>G		intron	N/A	ENSP00000392131.1
	CEP85L	ENST00000392500.7	TSL:1	c.242-2749C>G		intron	N/A	ENSP00000376288.3

Frequencies

GnomAD3 genomes AF: 0.0000725 AC: 11 AN: 151780 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000657

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00

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

GnomAD4 genome AF: 0.0000725 AC: 11 AN: 151780 Hom.: 0 Cov.: 31 AF XY: 0.0000945 AC XY: 7 AN XY: 74104

African (AFR) AF: 0.00 AC: 0 AN: 41320

American (AMR) AF: 0.0000657 AC: 1 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5198

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10468

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 67958

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.00 Hom.: 16

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.61
DANN	Benign	0.52
PhyloP100		-0.034

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: rs35407905; hg19: chr6-118890228;