chr6-118465476-T-C

Variant names:

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

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 306 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CEP85L	NM_001042475.3	c.2347A>G	p.Ile783Val	missense_variant	Exon 13 of 13	ENST00000368491.8	NP_001035940.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CEP85L	ENST00000368491.8	c.2347A>G	p.Ile783Val	missense_variant	Exon 13 of 13	1	NM_001042475.3	ENSP00000357477.3
CEP85L	ENST00000368488.9	c.2356A>G	p.Ile786Val	missense_variant	Exon 14 of 14	5		ENSP00000357474.5

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

GnomAD3 exomes AF: 0.000453 AC: 113 AN: 249336 Hom.: 0 AF XY: 0.000333 AC XY: 45 AN XY: 135270

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 SAS exome AF: 0.0000327

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

Gnomad4 AFR exome AF: 0.00658

Gnomad4 AMR exome AF: 0.000335

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 9.00e-7

Gnomad4 OTH exome AF: 0.000315

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

Gnomad4 AFR AF: 0.00707

Gnomad4 AMR AF: 0.000589

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000147

Gnomad4 OTH AF: 0.000945

Alfa AF: 0.000346 Hom.: 0

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

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Inborn genetic diseases Benign:1

Sep 30, 2021

Ambry Genetics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

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;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.0058	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.1	L;.
PrimateAI	Uncertain	0.56	T
PROVEAN	Benign	-0.50	N;N
REVEL	Benign	0.15
Sift	Benign	0.23	T;T
Sift4G	Benign	0.35	T;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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs181970377; hg19: chr6-118786639;