19-4416414-C-T

Variant names:

• chr19-4416414-C-T
• rs243359
• NM_005483.3:c.961-1606C>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.961-1606C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.291 in 152,090 control chromosomes in the GnomAD database, including 7,076 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 (7076 hom., cov: 32)
• Consequence: CHAF1A NM_005483.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.101
• Publications: 3 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.961-1606C>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.961-1606C>T		intron	N/A	ENSP00000301280.4	Q13111-1
	CHAF1A	ENST00000900275.1		c.1282-1606C>T		intron	N/A	ENSP00000570334.1
	CHAF1A	ENST00000926550.1		c.1111-1606C>T		intron	N/A	ENSP00000596609.1

Frequencies

GnomAD3 genomes AF: 0.291 AC: 44220 AN: 151972 Hom.: 7063 Cov.: 32

Gnomad AFR AF: 0.317

Gnomad AMI AF: 0.342

Gnomad AMR AF: 0.387

Gnomad ASJ AF: 0.261

Gnomad EAS AF: 0.596

Gnomad SAS AF: 0.363

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.310

Gnomad NFE AF: 0.223

Gnomad OTH AF: 0.288

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

GnomAD4 genome AF: 0.291 AC: 44263 AN: 152090 Hom.: 7076 Cov.: 32 AF XY: 0.299 AC XY: 22264 AN XY: 74354

African (AFR) AF: 0.317 AC: 13159 AN: 41524

American (AMR) AF: 0.389 AC: 5933 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.261 AC: 907 AN: 3470

East Asian (EAS) AF: 0.597 AC: 3074 AN: 5148

South Asian (SAS) AF: 0.363 AC: 1750 AN: 4822

European-Finnish (FIN) AF: 0.310 AC: 3273 AN: 10566

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

European-Non Finnish (NFE) AF: 0.223 AC: 15160 AN: 67978

Other (OTH) AF: 0.287 AC: 607 AN: 2112

Alfa AF: 0.259 Hom.: 8279

Bravo AF: 0.299

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	2.2
DANN	Benign	0.54
PhyloP100		0.10
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: rs243359; hg19: chr19-4416411;