chr6-118481924-G-A

Variant names:

• chr6-118481924-G-A
• rs1340109090
• NM_001042475.3:c.1600C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001042475.3(CEP85L):​c.1600C>T​(p.Leu534Leu) variant causes a synonymous change. The variant allele was found at a frequency of 0.00000072 in 1,388,314 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: CEP85L NM_001042475.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.83
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.4).

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.1600C>T	p.Leu534Leu	synonymous	Exon 8 of 13	NP_001035940.1	Q5SZL2-1
	CEP85L	NM_001178035.2		c.1609C>T	p.Leu537Leu	synonymous	Exon 9 of 14	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.1600C>T	p.Leu534Leu	synonymous	Exon 8 of 13	ENSP00000357477.3	Q5SZL2-1
	CEP85L	ENST00000434604.5	TSL:1	c.1609C>T	p.Leu537Leu	synonymous	Exon 9 of 9	ENSP00000392131.1	A2A3P3
	CEP85L	ENST00000368488.9	TSL:5	c.1609C>T	p.Leu537Leu	synonymous	Exon 9 of 14	ENSP00000357474.5	Q5SZL2-4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.20e-7 AC: 1 AN: 1388314 Hom.: 0 Cov.: 27 AF XY: 0.00 AC XY: 0 AN XY: 689346

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 30076

American (AMR) AF: 0.00 AC: 0 AN: 36120

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24446

East Asian (EAS) AF: 0.00 AC: 0 AN: 37114

South Asian (SAS) AF: 0.00 AC: 0 AN: 73036

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50322

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5524

European-Non Finnish (NFE) AF: 9.31e-7 AC: 1 AN: 1074652

Other (OTH) AF: 0.00 AC: 0 AN: 57024

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.40
CADD	Benign	7.9
DANN	Benign	0.60
PhyloP100		3.8

Splicing

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

Other links and lift over

dbSNP: rs1340109090; hg19: chr6-118803087;