Genetic Variant NM_152485.4:c.*2599T>C (chr1-209780226-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152485.4(C1orf74):c.*2599T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.441 in 301,396 control chromosomes in the GnomAD database, including 29,804 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 0.43 ( 14343 hom., cov: 33)

Exomes 𝑓: 0.45 ( 15461 hom. )

Consequence

C1orf74
NM_152485.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.251

Publications

10 publications found

Variant links:

Genes affected

C1orf74 (HGNC:26319): (chromosome 1 open reading frame 74)

C1orf74 links:

ENSG00000289700 (HGNC:):

ENSG00000289700 links:

TRAF3IP3 (HGNC:30766): (TRAF3 interacting protein 3) The gene encodes a protein that mediates cell growth by modulating the c-Jun N-terminal kinase signal transduction pathway. The encoded protein may also interact with a large multi-protein assembly containing the phosphatase 2A catalytic subunit. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2013]

TRAF3IP3 links:

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ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.535 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152485.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
C1orf74	NM_152485.4	MANE Select	c.*2599T>C	3_prime_UTR	Exon 2 of 2	NP_689698.1
TRAF3IP3	NM_025228.4	MANE Select	c.1313-244A>G	intron	N/A	NP_079504.2
TRAF3IP3	NM_001320143.2		c.1313-244A>G	intron	N/A	NP_001307072.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
C1orf74	ENST00000294811.2	TSL:1 MANE Select	c.*2599T>C	3_prime_UTR	Exon 2 of 2	ENSP00000294811.1
ENSG00000289700	ENST00000696133.1		c.*3423T>C	3_prime_UTR	Exon 10 of 10	ENSP00000512426.1
TRAF3IP3	ENST00000367025.8	TSL:1 MANE Select	c.1313-244A>G	intron	N/A	ENSP00000355992.3

Frequencies

GnomAD3 genomes

AF:

0.432

AC:

65596

AN:

151964

Hom.:

14330

Cov.:

show subpopulations

Gnomad AFR

AF:

0.397

Gnomad AMI

AF:

0.415

Gnomad AMR

AF:

0.485

Gnomad ASJ

AF:

0.511

Gnomad EAS

AF:

0.551

Gnomad SAS

AF:

0.439

Gnomad FIN

AF:

0.392

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.433

Gnomad OTH

AF:

0.444

GnomAD4 exome

AF:

0.450

AC:

67160

AN:

149314

Hom.:

15461

Cov.:

AF XY:

0.449

AC XY:

34593

AN XY:

76974

show subpopulations

African (AFR)

AF:

0.401

AC:

1980

AN:

4932

American (AMR)

AF:

0.482

AC:

2289

AN:

4752

Ashkenazi Jewish (ASJ)

AF:

0.528

AC:

3086

AN:

5842

East Asian (EAS)

AF:

0.613

AC:

7810

AN:

12738

South Asian (SAS)

AF:

0.464

AC:

1438

AN:

3102

European-Finnish (FIN)

AF:

0.373

AC:

3745

AN:

10050

Middle Eastern (MID)

AF:

0.488

AC:

381

AN:

780

European-Non Finnish (NFE)

AF:

0.432

AC:

41923

AN:

97126

Other (OTH)

AF:

0.451

AC:

4508

AN:

9992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1775

3550

5326

7101

8876

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

230

460

690

920

1150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.432

AC:

65642

AN:

152082

Hom.:

14343

Cov.:

AF XY:

0.431

AC XY:

32067

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.396

AC:

16447

AN:

41482

American (AMR)

AF:

0.485

AC:

7413

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.511

AC:

1771

AN:

3468

East Asian (EAS)

AF:

0.552

AC:

2858

AN:

5178

South Asian (SAS)

AF:

0.438

AC:

2113

AN:

4822

European-Finnish (FIN)

AF:

0.392

AC:

4141

AN:

10568

Middle Eastern (MID)

AF:

0.432

AC:

127

AN:

294

European-Non Finnish (NFE)

AF:

0.433

AC:

29454

AN:

67972

Other (OTH)

AF:

0.446

AC:

940

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1944

3888

5833

7777

9721

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

610

1220

1830

2440

3050

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.438

Hom.:

16859

Bravo

AF:

0.434

Asia WGS

AF:

0.475

AC:

1652

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

6.9

(source)

DANN

Benign

0.75

PhyloP100

0.25

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over