19-4405109-T-C

Variant names:

• chr19-4405109-T-C
• rs243341
• NM_005483.3:c.53-803T>C

Variant summary

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

The NM_005483.3(CHAF1A):​c.53-803T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,046 control chromosomes in the GnomAD database, including 8,723 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 (8723 hom., cov: 31)
• Consequence: CHAF1A NM_005483.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.86
• Publications: 7 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=-0.87).
• 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	c.53-803T>C		intron_variant	Intron 1 of 14	ENST00000301280.10	NP_005474.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CHAF1A	ENST00000301280.10	c.53-803T>C		intron_variant	Intron 1 of 14	1	NM_005483.3	ENSP00000301280.4
CHAF1A	ENST00000585854.1	c.52+2295T>C		intron_variant	Intron 1 of 1	2		ENSP00000465142.1
CHAF1A	ENST00000587580.1	n.114-803T>C		intron_variant	Intron 1 of 2	3

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49978 AN: 151928 Hom.: 8709 Cov.: 31

Gnomad AFR AF: 0.342

Gnomad AMI AF: 0.410

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.599

Gnomad SAS AF: 0.372

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.273

Gnomad OTH AF: 0.340

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

GnomAD4 genome AF: 0.329 AC: 50021 AN: 152046 Hom.: 8723 Cov.: 31 AF XY: 0.335 AC XY: 24916 AN XY: 74340

African (AFR) AF: 0.342 AC: 14179 AN: 41466

American (AMR) AF: 0.426 AC: 6490 AN: 15224

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1149 AN: 3470

East Asian (EAS) AF: 0.600 AC: 3103 AN: 5174

South Asian (SAS) AF: 0.372 AC: 1792 AN: 4816

European-Finnish (FIN) AF: 0.335 AC: 3550 AN: 10590

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.273 AC: 18561 AN: 67992

Other (OTH) AF: 0.339 AC: 714 AN: 2108

Alfa AF: 0.302 Hom.: 1119

Bravo AF: 0.338

Asia WGS AF: 0.466 AC: 1617 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.34
DANN	Benign	0.87
PhyloP100		-2.9
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: rs243341; hg19: chr19-4405106;