chr19-4405109-T-C

Position:

• chr19-4405109-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.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

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=-0.87).
• 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/exons	MANE	UniProt
CHAF1A	NM_005483.3	c.53-803T>C		intron_variant		ENST00000301280.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CHAF1A	ENST00000301280.10	c.53-803T>C		intron_variant		1	NM_005483.3	P1
CHAF1A	ENST00000585854.1	c.52+2295T>C		intron_variant		2
CHAF1A	ENST00000587580.1	n.114-803T>C		intron_variant, non_coding_transcript_variant		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

Gnomad4 AFR AF: 0.342

Gnomad4 AMR AF: 0.426

Gnomad4 ASJ AF: 0.331

Gnomad4 EAS AF: 0.600

Gnomad4 SAS AF: 0.372

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.273

Gnomad4 OTH AF: 0.339

Alfa AF: 0.301 Hom.: 1087

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

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: rs243341; hg19: chr19-4405106;