4-174304249-T-C

Variant names:

• chr4-174304249-T-C
• rs148050333
• NM_001040157.3:c.387T>C

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001040157.3(CEP44):​c.387T>C​(p.Ile129Ile) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00459 in 1,581,170 control chromosomes in the GnomAD database, including 31 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0038 (3 hom., cov: 32)
  • Exomes 𝑓: 0.0047 (28 hom.)
• Consequence: CEP44 NM_001040157.3 splice_region, synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.274
• Publications: 1 publications found

Genes affected

CEP44 (HGNC:29356): (centrosomal protein 44) Enables microtubule binding activity. Involved in centriole replication and centriole-centriole cohesion. Located in centriole; centrosome; and spindle pole. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 4-174304249-T-C is Benign according to our data. Variant chr4-174304249-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 2655190.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.274 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 3 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040157.3. 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
	CEP44	NM_001040157.3	MANE Select	c.387T>C	p.Ile129Ile	splice_region synonymous	Exon 6 of 12	NP_001035247.1	Q9C0F1-1
	CEP44	NM_001145314.2		c.387T>C	p.Ile129Ile	splice_region synonymous	Exon 6 of 11	NP_001138786.1	Q9C0F1-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CEP44	ENST00000503780.6	TSL:1 MANE Select	c.387T>C	p.Ile129Ile	splice_region synonymous	Exon 6 of 12	ENSP00000423153.1	Q9C0F1-1
	CEP44	ENST00000296519.6	TSL:1	c.387T>C	p.Ile129Ile	splice_region synonymous	Exon 4 of 10	ENSP00000296519.4	Q9C0F1-1
	CEP44	ENST00000396791.7	TSL:1	n.387T>C		splice_region non_coding_transcript_exon	Exon 6 of 14	ENSP00000380009.3	Q9C0F1-1

Frequencies

GnomAD3 genomes AF: 0.00385 AC: 586 AN: 152134 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.00125

Gnomad AMI AF: 0.0430

Gnomad AMR AF: 0.00576

Gnomad ASJ AF: 0.0135

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00145

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0222

Gnomad NFE AF: 0.00479

Gnomad OTH AF: 0.00384

GnomAD2 exomes AF: 0.00394 AC: 872 AN: 221376 AF XY: 0.00437

Gnomad AFR exome AF: 0.000908

Gnomad AMR exome AF: 0.00328

Gnomad ASJ exome AF: 0.0109

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00115

Gnomad NFE exome AF: 0.00552

Gnomad OTH exome AF: 0.00590

GnomAD4 exome AF: 0.00467 AC: 6675 AN: 1428918 Hom.: 28 Cov.: 30 AF XY: 0.00467 AC XY: 3318 AN XY: 710310

African (AFR) AF: 0.000578 AC: 18 AN: 31152

American (AMR) AF: 0.00372 AC: 127 AN: 34098

Ashkenazi Jewish (ASJ) AF: 0.0109 AC: 269 AN: 24710

East Asian (EAS) AF: 0.0000255 AC: 1 AN: 39184

South Asian (SAS) AF: 0.00184 AC: 145 AN: 78750

European-Finnish (FIN) AF: 0.00124 AC: 66 AN: 53092

Middle Eastern (MID) AF: 0.0103 AC: 58 AN: 5640

European-Non Finnish (NFE) AF: 0.00518 AC: 5713 AN: 1103368

Other (OTH) AF: 0.00472 AC: 278 AN: 58924

GnomAD4 genome AF: 0.00384 AC: 584 AN: 152252 Hom.: 3 Cov.: 32 AF XY: 0.00379 AC XY: 282 AN XY: 74446

African (AFR) AF: 0.00125 AC: 52 AN: 41562

American (AMR) AF: 0.00576 AC: 88 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0135 AC: 47 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.00145 AC: 7 AN: 4818

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10614

Middle Eastern (MID) AF: 0.0170 AC: 5 AN: 294

European-Non Finnish (NFE) AF: 0.00479 AC: 326 AN: 68006

Other (OTH) AF: 0.00380 AC: 8 AN: 2108

Alfa AF: 0.00531 Hom.: 2

Bravo AF: 0.00417

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.6
DANN	Benign	0.83
PhyloP100		0.27
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs148050333; hg19: chr4-175225400;