chr6-118635284-T-C

Variant names:

• chr6-118635284-T-C
• rs10484286
• NM_001042475.3:c.74-2673A>G

Variant summary

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

The NM_001178035.2(CEP85L):​c.83-2673A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.133 in 152,170 control chromosomes in the GnomAD database, including 1,728 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 0.13 (1728 hom., cov: 32)
• Consequence: CEP85L NM_001178035.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0820
• 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 = 0.181 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001178035.2. 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.74-2673A>G		intron	N/A	NP_001035940.1
	CEP85L	NM_001178035.2		c.83-2673A>G		intron	N/A	NP_001171506.1
	CEP85L	NM_206921.3		c.74-2673A>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.74-2673A>G		intron	N/A	ENSP00000357477.3
	CEP85L	ENST00000434604.5	TSL:1	c.83-2673A>G		intron	N/A	ENSP00000392131.1
	CEP85L	ENST00000392500.7	TSL:1	c.83-2673A>G		intron	N/A	ENSP00000376288.3

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20292 AN: 152052 Hom.: 1726 Cov.: 32

Gnomad AFR AF: 0.0319

Gnomad AMI AF: 0.235

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.201

Gnomad EAS AF: 0.0452

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.211

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.133 AC: 20302 AN: 152170 Hom.: 1728 Cov.: 32 AF XY: 0.135 AC XY: 10038 AN XY: 74384

African (AFR) AF: 0.0320 AC: 1330 AN: 41564

American (AMR) AF: 0.136 AC: 2082 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.201 AC: 699 AN: 3470

East Asian (EAS) AF: 0.0451 AC: 234 AN: 5192

South Asian (SAS) AF: 0.135 AC: 653 AN: 4820

European-Finnish (FIN) AF: 0.211 AC: 2232 AN: 10576

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12512 AN: 67946

Other (OTH) AF: 0.143 AC: 303 AN: 2112

Alfa AF: 0.162 Hom.: 301

Bravo AF: 0.123

Asia WGS AF: 0.0910 AC: 315 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.5
DANN	Benign	0.74
PhyloP100		-0.082
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: rs10484286; hg19: chr6-118956447;