Genetic Variant NM_145265.3:c.121+2431G>A (chr5-214298-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

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

The NM_145265.3(CCDC127):c.121+2431G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.386 in 151,998 control chromosomes in the GnomAD database, including 13,081 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 0.39 ( 13077 hom., cov: 31)

Exomes 𝑓: 0.60 ( 4 hom. )

Consequence

CCDC127
NM_145265.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.88

Publications

6 publications found

Variant links:

Genes affected

CCDC127 (HGNC:30520): (coiled-coil domain containing 127) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

CCDC127 links:

ENSG00000260774 (HGNC:):

ENSG00000260774 links:

Genome browser will be placed here

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=-1.01).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.503 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC127	NM_145265.3 link	c.121+2431G>A		intron_variant	Intron 2 of 2	ENST00000296824.4	NP_660308.1	Q96BQ5

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CCDC127	ENST00000296824.4 link	c.121+2431G>A	intron_variant	Intron 2 of 2	1	NM_145265.3	ENSP00000296824.2	Q96BQ5
ENSG00000260774	ENST00000565521.1 link	n.2481G>A	non_coding_transcript_exon_variant	Exon 2 of 2	2
CCDC127	ENST00000441693.2 link	c.121+2431G>A	intron_variant	Intron 1 of 1	2		ENSP00000411206.2	D6R9R2

Frequencies

GnomAD3 genomes

AF:

0.386

AC:

58650

AN:

151860

Hom.:

13081

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.381

Gnomad AMR

AF:

0.381

Gnomad ASJ

AF:

0.450

Gnomad EAS

AF:

0.281

Gnomad SAS

AF:

0.512

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.342

Gnomad NFE

AF:

0.508

Gnomad OTH

AF:

0.393

GnomAD4 exome

AF:

0.600

AC:

AN:

Hom.:

Cov.:

AF XY:

0.667

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AF:

0.750

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.563

AC:

AN:

Other (OTH)

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.386

AC:

58653

AN:

151978

Hom.:

13077

Cov.:

AF XY:

0.387

AC XY:

28765

AN XY:

74276

show subpopulations

African (AFR)

AF:

0.160

AC:

6634

AN:

41472

American (AMR)

AF:

0.381

AC:

5822

AN:

15266

Ashkenazi Jewish (ASJ)

AF:

0.450

AC:

1560

AN:

3470

East Asian (EAS)

AF:

0.281

AC:

1453

AN:

5166

South Asian (SAS)

AF:

0.512

AC:

2468

AN:

4820

European-Finnish (FIN)

AF:

0.471

AC:

4952

AN:

10524

Middle Eastern (MID)

AF:

0.316

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.508

AC:

34490

AN:

67944

Other (OTH)

AF:

0.395

AC:

834

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1690

3380

5071

6761

8451

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

568

1136

1704

2272

2840

<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:

0.432

Hom.:

1901

Bravo

AF:

0.362

Asia WGS

AF:

0.374

AC:

1298

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.020

(source)

DANN

Benign

0.47

PhyloP100

-2.9

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over