chr6-118481844-T-C

Variant names:

• chr6-118481844-T-C
• rs548222922
• NM_001042475.3:c.1680A>G

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_Strong BP6_Moderate BP7 BS2_Supporting

The NM_001042475.3(CEP85L):​c.1680A>G​(p.Gln560Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000689 in 1,597,566 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.000013 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: CEP85L NM_001042475.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.00500
• 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: Benign. The variant received -8 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP6: Variant 6-118481844-T-C is Benign according to our data. Variant chr6-118481844-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3026134.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.005 with no splicing effect.
• BS2: High AC in GnomAdExome4 at 9 AD gene. Variant has AC lower than other variant known as pathogenic in the gene, so the strength is limited to Supporting.

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.1680A>G	p.Gln560Gln	synonymous	Exon 8 of 13	NP_001035940.1	Q5SZL2-1
	CEP85L	NM_001178035.2		c.1689A>G	p.Gln563Gln	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.1680A>G	p.Gln560Gln	synonymous	Exon 8 of 13	ENSP00000357477.3	Q5SZL2-1
	CEP85L	ENST00000434604.5	TSL:1	c.1689A>G	p.Gln563Gln	synonymous	Exon 9 of 9	ENSP00000392131.1	A2A3P3
	CEP85L	ENST00000368488.9	TSL:5	c.1689A>G	p.Gln563Gln	synonymous	Exon 9 of 14	ENSP00000357474.5	Q5SZL2-4

Frequencies

GnomAD3 genomes AF: 0.0000131 AC: 2 AN: 152106 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00000840 AC: 2 AN: 238192 AF XY: 0.00000773

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000623 AC: 9 AN: 1445342 Hom.: 0 Cov.: 27 AF XY: 0.00000834 AC XY: 6 AN XY: 719066

African (AFR) AF: 0.00 AC: 0 AN: 32778

American (AMR) AF: 0.00 AC: 0 AN: 43570

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25856

East Asian (EAS) AF: 0.00 AC: 0 AN: 39154

South Asian (SAS) AF: 0.0000957 AC: 8 AN: 83608

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52854

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5680

European-Non Finnish (NFE) AF: 9.07e-7 AC: 1 AN: 1102152

Other (OTH) AF: 0.00 AC: 0 AN: 59690

GnomAD4 genome AF: 0.0000131 AC: 2 AN: 152224 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41568

American (AMR) AF: 0.00 AC: 0 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10582

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2108

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	5.7
DANN	Benign	0.63
PhyloP100		-0.0050

Splicing

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

Other links and lift over

dbSNP: rs548222922; hg19: chr6-118803007;