NM_138363.3:c.149-11T>C

Variant names:

• chr17-64510162-T-C
• rs57166100
• NM_138363.3:c.149-11T>C

Variant summary

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

The NM_138363.3(CEP95):​c.149-11T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0554 in 1,446,602 control chromosomes in the GnomAD database, including 4,562 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 0.13 (2188 hom., cov: 31)
  • Exomes 𝑓: 0.047 (2374 hom.)
• Consequence: CEP95 NM_138363.3 intron
• Scores: Splicing: ADA: 0.00009177
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.09
• Publications: 7 publications found

Genes affected

CEP95 (HGNC:25141): (centrosomal protein 95) Located in centrosome and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_138363.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP95	NM_138363.3	MANE Select	c.149-11T>C		intron	N/A	NP_612372.1
	CEP95	NM_001316990.2		c.-238-11T>C		intron	N/A	NP_001303919.1
	CEP95	NR_133644.2		n.270-11T>C		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP95	ENST00000556440.7	TSL:1 MANE Select	c.149-11T>C		intron	N/A	ENSP00000450461.2
	CEP95	ENST00000553956.6	TSL:1	n.149-11T>C		intron	N/A	ENSP00000452317.2
	CEP95	ENST00000581056.5	TSL:2	c.149-11T>C		intron	N/A	ENSP00000462189.1

Frequencies

GnomAD3 genomes AF: 0.127 AC: 18875 AN: 148834 Hom.: 2178 Cov.: 31

Gnomad AFR AF: 0.304

Gnomad AMI AF: 0.0356

Gnomad AMR AF: 0.164

Gnomad ASJ AF: 0.0453

Gnomad EAS AF: 0.0394

Gnomad SAS AF: 0.0359

Gnomad FIN AF: 0.0456

Gnomad MID AF: 0.0705

Gnomad NFE AF: 0.0423

Gnomad OTH AF: 0.0948

GnomAD2 exomes AF: 0.0722 AC: 14806 AN: 205170 AF XY: 0.0638

Gnomad AFR exome AF: 0.295

Gnomad AMR exome AF: 0.156

Gnomad ASJ exome AF: 0.0403

Gnomad EAS exome AF: 0.0409

Gnomad FIN exome AF: 0.0476

Gnomad NFE exome AF: 0.0402

Gnomad OTH exome AF: 0.0608

GnomAD4 exome AF: 0.0472 AC: 61284 AN: 1297664 Hom.: 2374 Cov.: 21 AF XY: 0.0458 AC XY: 29789 AN XY: 649790

African (AFR) AF: 0.282 AC: 8309 AN: 29422

American (AMR) AF: 0.150 AC: 6080 AN: 40488

Ashkenazi Jewish (ASJ) AF: 0.0402 AC: 977 AN: 24276

East Asian (EAS) AF: 0.0396 AC: 1530 AN: 38670

South Asian (SAS) AF: 0.0329 AC: 2639 AN: 80216

European-Finnish (FIN) AF: 0.0479 AC: 2464 AN: 51394

Middle Eastern (MID) AF: 0.0465 AC: 257 AN: 5526

European-Non Finnish (NFE) AF: 0.0370 AC: 36004 AN: 972866

Other (OTH) AF: 0.0552 AC: 3024 AN: 54806

GnomAD4 genome AF: 0.127 AC: 18921 AN: 148938 Hom.: 2188 Cov.: 31 AF XY: 0.127 AC XY: 9199 AN XY: 72710

African (AFR) AF: 0.304 AC: 12412 AN: 40832

American (AMR) AF: 0.164 AC: 2467 AN: 15052

Ashkenazi Jewish (ASJ) AF: 0.0453 AC: 155 AN: 3424

East Asian (EAS) AF: 0.0394 AC: 203 AN: 5158

South Asian (SAS) AF: 0.0362 AC: 171 AN: 4730

European-Finnish (FIN) AF: 0.0456 AC: 466 AN: 10230

Middle Eastern (MID) AF: 0.0764 AC: 22 AN: 288

European-Non Finnish (NFE) AF: 0.0423 AC: 2801 AN: 66278

Other (OTH) AF: 0.0938 AC: 192 AN: 2048

Alfa AF: 0.0979 Hom.: 419

Bravo AF: 0.141

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.82
DANN	Benign	0.46
PhyloP100		-1.1
PromoterAI		0.0052	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000092
dbscSNV1_RF	Benign	0.0020
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs57166100; hg19: chr17-62506280; COSMIC: COSV56748206; COSMIC: COSV56748206;