chr6-118537016-A-G

Variant names:

• chr6-118537016-A-G
• rs10484287
• NM_001042475.3:c.1021-13096T>C

Variant summary

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

The NM_001042475.3(CEP85L):​c.1021-13096T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.709 in 151,976 control chromosomes in the GnomAD database, including 38,890 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 0.71 (38890 hom., cov: 31)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.28
• 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.1021-13096T>C		intron_variant	Intron 3 of 12	ENST00000368491.8	NP_001035940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8	c.1021-13096T>C		intron_variant	Intron 3 of 12	1	NM_001042475.3	ENSP00000357477.3

Frequencies

GnomAD3 genomes AF: 0.709 AC: 107628 AN: 151858 Hom.: 38854 Cov.: 31

Gnomad AFR AF: 0.750

Gnomad AMI AF: 0.679

Gnomad AMR AF: 0.539

Gnomad ASJ AF: 0.700

Gnomad EAS AF: 0.353

Gnomad SAS AF: 0.663

Gnomad FIN AF: 0.743

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.749

Gnomad OTH AF: 0.670

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

GnomAD4 genome AF: 0.709 AC: 107710 AN: 151976 Hom.: 38890 Cov.: 31 AF XY: 0.702 AC XY: 52170 AN XY: 74298

African (AFR) AF: 0.750 AC: 31114 AN: 41470

American (AMR) AF: 0.538 AC: 8207 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.700 AC: 2426 AN: 3468

East Asian (EAS) AF: 0.353 AC: 1827 AN: 5172

South Asian (SAS) AF: 0.664 AC: 3191 AN: 4806

European-Finnish (FIN) AF: 0.743 AC: 7847 AN: 10562

Middle Eastern (MID) AF: 0.748 AC: 220 AN: 294

European-Non Finnish (NFE) AF: 0.749 AC: 50850 AN: 67928

Other (OTH) AF: 0.668 AC: 1409 AN: 2108

Alfa AF: 0.743 Hom.: 5466

Bravo AF: 0.689

Asia WGS AF: 0.532 AC: 1847 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.32
DANN	Benign	0.35
PhyloP100		-1.3
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: rs10484287; hg19: chr6-118858179; COSMIC: COSV63827571;