rs11752626

Variant names:

• chr6-118467489-G-T
• rs11752626
• NM_001042475.3:c.2254+1583C>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.2254+1583C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.35 in 151,868 control chromosomes in the GnomAD database, including 10,318 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 0.35 (10318 hom., cov: 31)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.300
• Publications: 14 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: Labcorp Genetics (formerly Invitae), G2P, ClinGen
• 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.45 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	NM_001042475.3	MANE Select	c.2254+1583C>A		intron	N/A	NP_001035940.1	Q5SZL2-1
	CEP85L	NM_001178035.2		c.2263+1583C>A		intron	N/A	NP_001171506.1	Q5SZL2-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	ENST00000368491.8	TSL:1 MANE Select	c.2254+1583C>A		intron	N/A	ENSP00000357477.3	Q5SZL2-1
	CEP85L	ENST00000368488.9	TSL:5	c.2263+1583C>A		intron	N/A	ENSP00000357474.5	Q5SZL2-4
	CEP85L	ENST00000875590.1		c.2101+1583C>A		intron	N/A	ENSP00000545649.1

Frequencies

GnomAD3 genomes AF: 0.350 AC: 53184 AN: 151752 Hom.: 10318 Cov.: 31

Gnomad AFR AF: 0.195

Gnomad AMI AF: 0.374

Gnomad AMR AF: 0.265

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.282

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.434

Gnomad MID AF: 0.424

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.319

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

GnomAD4 genome AF: 0.350 AC: 53200 AN: 151868 Hom.: 10318 Cov.: 31 AF XY: 0.346 AC XY: 25666 AN XY: 74172

African (AFR) AF: 0.195 AC: 8096 AN: 41438

American (AMR) AF: 0.264 AC: 4022 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1270 AN: 3460

East Asian (EAS) AF: 0.282 AC: 1456 AN: 5164

South Asian (SAS) AF: 0.366 AC: 1761 AN: 4808

European-Finnish (FIN) AF: 0.434 AC: 4576 AN: 10546

Middle Eastern (MID) AF: 0.439 AC: 129 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30874 AN: 67896

Other (OTH) AF: 0.320 AC: 675 AN: 2108

Alfa AF: 0.410 Hom.: 2809

Bravo AF: 0.330

Asia WGS AF: 0.304 AC: 1056 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.1
DANN	Benign	0.39
PhyloP100		0.30
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: rs11752626; hg19: chr6-118788652; COSMIC: COSV63824108;