Genetic Variant NM_005483.3: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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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