Genetic Variant CHAF1A:c.*24T>C (chr19-4443049-T-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_005483.3(CHAF1A):c.*24T>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 0.308 in 1,425,146 control chromosomes in the GnomAD database, including 71,557 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 0.33 ( 8630 hom., cov: 33)

Exomes 𝑓: 0.31 ( 62927 hom. )

Consequence

CHAF1A
NM_005483.3 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.41

Publications

30 publications found

Variant links:

Genes affected

CHAF1A (HGNC:1910): (chromatin assembly factor 1 subunit A) Chromatin assembly factor I (CAF1) is a nuclear complex consisting of p50, p60 (CHAF1B; MIM 601245), and p150 (CHAF1A) subunits that assembles histone octamers onto replicating DNA in vitro (Kaufman et al., 1995 [PubMed 7600578]).[supplied by OMIM, Mar 2008]

CHAF1A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.126).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.582 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CHAF1A	NM_005483.3 link	c.*24T>C		3_prime_UTR_variant	Exon 15 of 15	ENST00000301280.10	NP_005474.2	Q13111-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAF1A	ENST00000301280.10 link	c.*24T>C		3_prime_UTR_variant	Exon 15 of 15	1	NM_005483.3	ENSP00000301280.4		Q13111-1
CHAF1A	ENST00000589648.1 link	c.88+708T>C		intron_variant	Intron 1 of 1	5		ENSP00000466475.1		K7EME9

Frequencies

GnomAD3 genomes

AF:

0.327

AC:

49715

AN:

151966

Hom.:

8616

Cov.:

show subpopulations

Gnomad AFR

AF:

0.331

Gnomad AMI

AF:

0.409

Gnomad AMR

AF:

0.427

Gnomad ASJ

AF:

0.332

Gnomad EAS

AF:

0.599

Gnomad SAS

AF:

0.371

Gnomad FIN

AF:

0.336

Gnomad MID

AF:

0.373

Gnomad NFE

AF:

0.275

Gnomad OTH

AF:

0.342

GnomAD2 exomes

AF:

0.364

AC:

62847

AN:

172860

AF XY:

0.356

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.527

Gnomad ASJ exome

AF:

0.344

Gnomad EAS exome

AF:

0.589

Gnomad FIN exome

AF:

0.331

Gnomad NFE exome

AF:

0.284

Gnomad OTH exome

AF:

0.338

GnomAD4 exome

AF:

0.306

AC:

389397

AN:

1273062

Hom.:

62927

Cov.:

AF XY:

0.306

AC XY:

194533

AN XY:

635432

show subpopulations

African (AFR)

AF:

0.336

AC:

10052

AN:

29878

American (AMR)

AF:

0.508

AC:

18365

AN:

36152

Ashkenazi Jewish (ASJ)

AF:

0.351

AC:

8556

AN:

24402

East Asian (EAS)

AF:

0.619

AC:

22663

AN:

36598

South Asian (SAS)

AF:

0.352

AC:

27230

AN:

77368

European-Finnish (FIN)

AF:

0.335

AC:

16780

AN:

50108

Middle Eastern (MID)

AF:

0.355

AC:

1932

AN:

5446

European-Non Finnish (NFE)

AF:

0.278

AC:

266172

AN:

958940

Other (OTH)

AF:

0.326

AC:

17647

AN:

54170

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

12159

24318

36477

48636

60795

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8912

17824

26736

35648

44560

<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:

0.327

AC:

49757

AN:

152084

Hom.:

8630

Cov.:

AF XY:

0.333

AC XY:

24757

AN XY:

74346

show subpopulations

African (AFR)

AF:

0.330

AC:

13694

AN:

41466

American (AMR)

AF:

0.428

AC:

6548

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.332

AC:

1151

AN:

3472

East Asian (EAS)

AF:

0.600

AC:

3100

AN:

5168

South Asian (SAS)

AF:

0.371

AC:

1791

AN:

4826

European-Finnish (FIN)

AF:

0.336

AC:

3560

AN:

10590

Middle Eastern (MID)

AF:

0.363

AC:

106

AN:

292

European-Non Finnish (NFE)

AF:

0.275

AC:

18717

AN:

67964

Other (OTH)

AF:

0.340

AC:

718

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1738

3475

5213

6950

8688

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

486

972

1458

1944

2430

<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:

0.304

Hom.:

8404

Bravo

AF:

0.336

Asia WGS

AF:

0.463

AC:

1608

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.16

(source)

DANN

Benign

0.47

PhyloP100

-2.4

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