19-4415455-C-T

Variant names:

• chr19-4415455-C-T
• rs243356
• NM_005483.3:c.961-2565C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005483.3(CHAF1A):​c.961-2565C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.292 in 151,974 control chromosomes in the GnomAD database, including 7,125 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 0.29 (7125 hom., cov: 31)
• Consequence: CHAF1A NM_005483.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.38
• Publications: 9 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 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.961-2565C>T		intron	N/A	NP_005474.2	Q13111-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CHAF1A	ENST00000301280.10	TSL:1 MANE Select	c.961-2565C>T		intron	N/A	ENSP00000301280.4	Q13111-1
	CHAF1A	ENST00000900275.1		c.1282-2565C>T		intron	N/A	ENSP00000570334.1
	CHAF1A	ENST00000926550.1		c.1111-2565C>T		intron	N/A	ENSP00000596609.1

Frequencies

GnomAD3 genomes AF: 0.292 AC: 44349 AN: 151854 Hom.: 7112 Cov.: 31

Gnomad AFR AF: 0.321

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.312

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.290

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.292 AC: 44391 AN: 151974 Hom.: 7125 Cov.: 31 AF XY: 0.300 AC XY: 22314 AN XY: 74280

African (AFR) AF: 0.320 AC: 13279 AN: 41450

American (AMR) AF: 0.390 AC: 5947 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 907 AN: 3472

East Asian (EAS) AF: 0.598 AC: 3078 AN: 5150

South Asian (SAS) AF: 0.363 AC: 1750 AN: 4820

European-Finnish (FIN) AF: 0.309 AC: 3262 AN: 10546

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.223 AC: 15157 AN: 67964

Other (OTH) AF: 0.289 AC: 609 AN: 2108

Alfa AF: 0.249 Hom.: 2647

Bravo AF: 0.300

Asia WGS AF: 0.453 AC: 1571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
CADD	Benign	0.90
DANN	Benign	0.75
PhyloP100		-1.4
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: rs243356; hg19: chr19-4415452;