rs6906287

Variant names:

• chr6-118641577-T-C
• rs6906287
• NM_001042475.3:c.74-8966A>G

Variant summary

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

The NM_001042475.3(CEP85L):​c.74-8966A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 152,002 control chromosomes in the GnomAD database, including 10,864 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 0.36 (10864 hom., cov: 31)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.162
• Publications: 21 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.453 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.74-8966A>G		intron	N/A	NP_001035940.1	Q5SZL2-1
	CEP85L	NM_001178035.2		c.83-8966A>G		intron	N/A	NP_001171506.1	Q5SZL2-4
	CEP85L	NM_206921.3		c.74-8966A>G		intron	N/A	NP_996804.2	Q5SZL2-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP85L	ENST00000368491.8	TSL:1 MANE Select	c.74-8966A>G		intron	N/A	ENSP00000357477.3	Q5SZL2-1
	CEP85L	ENST00000434604.5	TSL:1	c.83-8966A>G		intron	N/A	ENSP00000392131.1	A2A3P3
	CEP85L	ENST00000392500.7	TSL:1	c.83-8966A>G		intron	N/A	ENSP00000376288.3	Q5SZL2-2

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55318 AN: 151884 Hom.: 10865 Cov.: 31

Gnomad AFR AF: 0.237

Gnomad AMI AF: 0.407

Gnomad AMR AF: 0.269

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.366

Gnomad FIN AF: 0.444

Gnomad MID AF: 0.434

Gnomad NFE AF: 0.457

Gnomad OTH AF: 0.330

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

GnomAD4 genome AF: 0.364 AC: 55333 AN: 152002 Hom.: 10864 Cov.: 31 AF XY: 0.360 AC XY: 26703 AN XY: 74270

African (AFR) AF: 0.237 AC: 9822 AN: 41480

American (AMR) AF: 0.268 AC: 4101 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1266 AN: 3464

East Asian (EAS) AF: 0.283 AC: 1461 AN: 5170

South Asian (SAS) AF: 0.367 AC: 1766 AN: 4818

European-Finnish (FIN) AF: 0.444 AC: 4691 AN: 10556

Middle Eastern (MID) AF: 0.449 AC: 132 AN: 294

European-Non Finnish (NFE) AF: 0.457 AC: 31026 AN: 67926

Other (OTH) AF: 0.331 AC: 698 AN: 2108

Alfa AF: 0.418 Hom.: 25473

Bravo AF: 0.345

Asia WGS AF: 0.306 AC: 1063 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.4
DANN	Benign	0.35
PhyloP100		0.16
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: rs6906287; hg19: chr6-118962740;