rs2992

chr19-4443049-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.41

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• 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/exons	MANE	UniProt
CHAF1A	NM_005483.3	c.*24T>C		3_prime_UTR_variant	15/15	ENST00000301280.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAF1A	ENST00000301280.10	c.*24T>C		3_prime_UTR_variant	15/15	1	NM_005483.3	P1
CHAF1A	ENST00000589648.1	c.88+708T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.327 AC: 49715 AN: 151966 Hom.: 8616 Cov.: 33

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

GnomAD3 exomes AF: 0.364 AC: 62847 AN: 172860 Hom.: 12384 AF XY: 0.356 AC XY: 32463 AN XY: 91116

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 SAS exome AF: 0.348

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.: 19 AF XY: 0.306 AC XY: 194533 AN XY: 635432

Gnomad4 AFR exome AF: 0.336

Gnomad4 AMR exome AF: 0.508

Gnomad4 ASJ exome AF: 0.351

Gnomad4 EAS exome AF: 0.619

Gnomad4 SAS exome AF: 0.352

Gnomad4 FIN exome AF: 0.335

Gnomad4 NFE exome AF: 0.278

Gnomad4 OTH exome AF: 0.326

GnomAD4 genome AF: 0.327 AC: 49757 AN: 152084 Hom.: 8630 Cov.: 33 AF XY: 0.333 AC XY: 24757 AN XY: 74346

Gnomad4 AFR AF: 0.330

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.332

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.371

Gnomad4 FIN AF: 0.336

Gnomad4 NFE AF: 0.275

Gnomad4 OTH AF: 0.340

Alfa AF: 0.298 Hom.: 5961

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
Dann	Benign	0.47

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

LitVar

Other links and lift over

dbSNP: rs2992; hg19: chr19-4443046;