rs11756438

Variant names:

• chr6-118672469-C-A
• rs11756438
• ENST00000434604.5:c.-27-19661G>T

Variant summary

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

The ENST00000434604.5(CEP85L):​c.-27-19661G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.414 in 151,784 control chromosomes in the GnomAD database, including 13,262 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 0.41 (13262 hom., cov: 33)
• Consequence: CEP85L ENST00000434604.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 40 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

LOC124901388 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001178035.2	c.-27-19661G>T		intron_variant	Intron 1 of 13		NP_001171506.1
CEP85L	XM_017010846.2	c.-138-7948G>T		intron_variant	Intron 1 of 14		XP_016866335.1
CEP85L	XM_047418758.1	c.-27-19661G>T		intron_variant	Intron 2 of 14		XP_047274714.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000434604.5	c.-27-19661G>T		intron_variant	Intron 1 of 8	1		ENSP00000392131.1
CEP85L	ENST00000392500.7	c.-138-7948G>T		intron_variant	Intron 1 of 7	1		ENSP00000376288.3
CEP85L	ENST00000368488.9	c.-27-19661G>T		intron_variant	Intron 1 of 13	5		ENSP00000357474.5

Frequencies

GnomAD3 genomes AF: 0.414 AC: 62854 AN: 151668 Hom.: 13254 Cov.: 33

Gnomad AFR AF: 0.382

Gnomad AMI AF: 0.430

Gnomad AMR AF: 0.309

Gnomad ASJ AF: 0.367

Gnomad EAS AF: 0.275

Gnomad SAS AF: 0.373

Gnomad FIN AF: 0.443

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.382

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

GnomAD4 genome AF: 0.414 AC: 62888 AN: 151784 Hom.: 13262 Cov.: 33 AF XY: 0.408 AC XY: 30283 AN XY: 74166

African (AFR) AF: 0.382 AC: 15808 AN: 41392

American (AMR) AF: 0.308 AC: 4700 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.367 AC: 1274 AN: 3468

East Asian (EAS) AF: 0.275 AC: 1419 AN: 5158

South Asian (SAS) AF: 0.373 AC: 1798 AN: 4818

European-Finnish (FIN) AF: 0.443 AC: 4640 AN: 10482

Middle Eastern (MID) AF: 0.514 AC: 149 AN: 290

European-Non Finnish (NFE) AF: 0.470 AC: 31903 AN: 67892

Other (OTH) AF: 0.382 AC: 807 AN: 2110

Alfa AF: 0.447 Hom.: 24543

Bravo AF: 0.404

Asia WGS AF: 0.318 AC: 1103 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.63
DANN	Benign	0.47
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: rs11756438; hg19: chr6-118993632; COSMIC: COSV63827892;