NM_001042475.3:c.2347A>G

Variant names:

• chr6-118465476-T-C
• rs181970377
• NM_001042475.3:c.2347A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001042475.3(CEP85L):​c.2347A>G​(p.Ile783Val) variant causes a missense change. The variant allele was found at a frequency of 0.000349 in 1,613,710 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0020 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00018 (1 hom.)
• Consequence: CEP85L NM_001042475.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.94
• Publications: 4 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: ClinGen, Labcorp Genetics (formerly Invitae), PanelApp Australia, G2P
• lissencephaly due to LIS1 mutation

  Inheritance: AD Classification: STRONG Submitted by: Illumina

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0058429837).
• BP6: Variant 6-118465476-T-C is Benign according to our data. Variant chr6-118465476-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2395238.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00201 (306/152296) while in subpopulation AFR AF = 0.00707 (294/41556). AF 95% confidence interval is 0.00641. There are 0 homozygotes in GnomAd4. There are 146 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High AC in GnomAd4 at 306 AD gene.

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.2347A>G	p.Ile783Val	missense	Exon 13 of 13	NP_001035940.1	Q5SZL2-1
	CEP85L	NM_001178035.2		c.2356A>G	p.Ile786Val	missense	Exon 14 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.2347A>G	p.Ile783Val	missense	Exon 13 of 13	ENSP00000357477.3	Q5SZL2-1
	CEP85L	ENST00000368488.9	TSL:5	c.2356A>G	p.Ile786Val	missense	Exon 14 of 14	ENSP00000357474.5	Q5SZL2-4
	CEP85L	ENST00000875590.1		c.2194A>G	p.Ile732Val	missense	Exon 12 of 12	ENSP00000545649.1

Frequencies

GnomAD3 genomes AF: 0.00200 AC: 304 AN: 152178 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00705

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000589

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000147

Gnomad OTH AF: 0.000955

GnomAD2 exomes AF: 0.000453 AC: 113 AN: 249336 AF XY: 0.000333

Gnomad AFR exome AF: 0.00652

Gnomad AMR exome AF: 0.000290

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: 0.000165

GnomAD4 exome AF: 0.000176 AC: 257 AN: 1461414 Hom.: 1 Cov.: 31 AF XY: 0.000146 AC XY: 106 AN XY: 727026

African (AFR) AF: 0.00658 AC: 220 AN: 33460

American (AMR) AF: 0.000335 AC: 15 AN: 44716

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39686

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.000173 AC: 1 AN: 5764

European-Non Finnish (NFE) AF: 9.00e-7 AC: 1 AN: 1111670

Other (OTH) AF: 0.000315 AC: 19 AN: 60382

GnomAD4 genome AF: 0.00201 AC: 306 AN: 152296 Hom.: 0 Cov.: 32 AF XY: 0.00196 AC XY: 146 AN XY: 74480

African (AFR) AF: 0.00707 AC: 294 AN: 41556

American (AMR) AF: 0.000589 AC: 9 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

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

European-Non Finnish (NFE) AF: 0.0000147 AC: 1 AN: 68026

Other (OTH) AF: 0.000945 AC: 2 AN: 2116

Alfa AF: 0.000644 Hom.: 2

Bravo AF: 0.00232

ESP6500AA AF: 0.00543 AC: 22

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.000538 AC: 65

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.0085	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.80	T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.0058	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L
PhyloP100		4.9
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.50	N
REVEL	Benign	0.15
Sift	Benign	0.23	T
Sift4G	Benign	0.35	T
Polyphen		1.0	D
Vest4		0.30
MVP		0.44
MPC		0.41
ClinPred		0.043	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.12
gMVP		0.23
Mutation Taster		=83/17	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs181970377; hg19: chr6-118786639;