rs724868

Variant names:

• chr6-118473989-C-T
• rs724868
• NM_001042475.3:c.1915-3345G>A

Variant summary

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

The NM_001178035.2(CEP85L):​c.1924-3345G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,090 control chromosomes in the GnomAD database, including 1,785 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 0.14 (1785 hom., cov: 32)
• Consequence: CEP85L NM_001178035.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.192
• Publications: 8 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

ENSG00000303332 (HGNC:):

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 (NFE) allele frequency at 95% confidence interval = 0.183 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	NM_001042475.3	MANE Select	c.1915-3345G>A		intron	N/A	NP_001035940.1
	CEP85L	NM_001178035.2		c.1924-3345G>A		intron	N/A	NP_001171506.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	ENST00000368491.8	TSL:1 MANE Select	c.1915-3345G>A		intron	N/A	ENSP00000357477.3
	CEP85L	ENST00000368488.9	TSL:5	c.1924-3345G>A		intron	N/A	ENSP00000357474.5
	CEP85L	ENST00000875590.1		c.1762-3345G>A		intron	N/A	ENSP00000545649.1

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20669 AN: 151972 Hom.: 1783 Cov.: 32

Gnomad AFR AF: 0.0360

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.202

Gnomad EAS AF: 0.0461

Gnomad SAS AF: 0.134

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.186

Gnomad OTH AF: 0.144

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

GnomAD4 genome AF: 0.136 AC: 20684 AN: 152090 Hom.: 1785 Cov.: 32 AF XY: 0.138 AC XY: 10250 AN XY: 74344

African (AFR) AF: 0.0362 AC: 1505 AN: 41542

American (AMR) AF: 0.136 AC: 2077 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.202 AC: 700 AN: 3466

East Asian (EAS) AF: 0.0460 AC: 238 AN: 5170

South Asian (SAS) AF: 0.135 AC: 650 AN: 4810

European-Finnish (FIN) AF: 0.219 AC: 2308 AN: 10558

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

European-Non Finnish (NFE) AF: 0.186 AC: 12614 AN: 67970

Other (OTH) AF: 0.144 AC: 304 AN: 2106

Alfa AF: 0.165 Hom.: 301

Bravo AF: 0.125

Asia WGS AF: 0.0910 AC: 317 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	2.5
DANN	Benign	0.63
PhyloP100		-0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs724868; hg19: chr6-118795152;