6-118486684-C-T

Variant names:

• chr6-118486684-C-T
• rs25422
• NM_001042475.3:c.1438-2826G>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.1438-2826G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.174 in 152,104 control chromosomes in the GnomAD database, including 2,430 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 0.17 (2430 hom., cov: 32)
• Consequence: CEP85L NM_001042475.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.745
• 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: G2P, Labcorp Genetics (formerly Invitae), PanelApp Australia
• lissencephaly due to LIS1 mutation

  Inheritance: AD Classification: STRONG Submitted by: Illumina

LOC105377971 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.1438-2826G>A		intron_variant	Intron 6 of 12	ENST00000368491.8	NP_001035940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8	c.1438-2826G>A		intron_variant	Intron 6 of 12	1	NM_001042475.3	ENSP00000357477.3
CEP85L	ENST00000434604.5	c.1447-2826G>A		intron_variant	Intron 7 of 8	1		ENSP00000392131.1
CEP85L	ENST00000368488.9	c.1447-2826G>A		intron_variant	Intron 7 of 13	5		ENSP00000357474.5

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26497 AN: 151986 Hom.: 2424 Cov.: 32

Gnomad AFR AF: 0.154

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.156

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0517

Gnomad SAS AF: 0.140

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.192

Gnomad OTH AF: 0.179

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

GnomAD4 genome AF: 0.174 AC: 26525 AN: 152104 Hom.: 2430 Cov.: 32 AF XY: 0.175 AC XY: 12992 AN XY: 74336

African (AFR) AF: 0.154 AC: 6409 AN: 41500

American (AMR) AF: 0.156 AC: 2382 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 766 AN: 3470

East Asian (EAS) AF: 0.0516 AC: 267 AN: 5176

South Asian (SAS) AF: 0.141 AC: 678 AN: 4824

European-Finnish (FIN) AF: 0.218 AC: 2308 AN: 10576

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.192 AC: 13036 AN: 67978

Other (OTH) AF: 0.179 AC: 378 AN: 2110

Alfa AF: 0.184 Hom.: 11698

Bravo AF: 0.169

Asia WGS AF: 0.117 AC: 406 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.20
DANN	Benign	0.15
PhyloP100		-0.74
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: rs25422; hg19: chr6-118807847;