chr19-4443049-T-C

Variant names:

• chr19-4443049-T-C
• rs2992
• NM_005483.3:c.*24T>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate 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
• Publications: 30 publications found

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

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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005483.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAF1A	NM_005483.3	MANE Select	c.*24T>C		3_prime_UTR	Exon 15 of 15	NP_005474.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAF1A	ENST00000301280.10	TSL:1 MANE Select	c.*24T>C		3_prime_UTR	Exon 15 of 15	ENSP00000301280.4
	CHAF1A	ENST00000900275.1		c.*24T>C		3_prime_UTR	Exon 17 of 17	ENSP00000570334.1
	CHAF1A	ENST00000926550.1		c.*24T>C		3_prime_UTR	Exon 17 of 17	ENSP00000596609.1

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

GnomAD2 exomes AF: 0.364 AC: 62847 AN: 172860 AF XY: 0.356

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

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

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

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

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.47
PhyloP100		-2.4
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2992; hg19: chr19-4443046;