19-32973319-C-T

Variant names:

• chr19-32973319-C-T
• rs73037453
• NM_152266.5:c.106+17C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152266.5(FAAP24):​c.106+17C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 1,612,610 control chromosomes in the GnomAD database, including 26,309 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.18 (2751 hom., cov: 32)
  • Exomes 𝑓: 0.17 (23558 hom.)
• Consequence: FAAP24 NM_152266.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0470

Genes affected

FAAP24 (HGNC:28467): (FA core complex associated protein 24) FAAP24 is a component of the Fanconi anemia (FA) core complex (see MIM 227650), which plays a crucial role in DNA damage response (Ciccia et al., 2007 [PubMed 17289582]).[supplied by OMIM, Mar 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 19-32973319-C-T is Benign according to our data. Variant chr19-32973319-C-T is described in ClinVar as [Benign]. Clinvar id is 2688491.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.242 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAAP24	NM_152266.5	c.106+17C>T		intron_variant	Intron 2 of 4	ENST00000588258.6	NP_689479.1
FAAP24	NM_001300978.2	c.-42-741C>T		intron_variant	Intron 1 of 2		NP_001287907.1
FAAP24	XM_005259393.4	c.35+17C>T		intron_variant	Intron 2 of 4		XP_005259450.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAAP24	ENST00000588258.6	c.106+17C>T		intron_variant	Intron 2 of 4	1	NM_152266.5	ENSP00000466121.1

Frequencies

GnomAD3 genomes AF: 0.180 AC: 27325 AN: 151916 Hom.: 2745 Cov.: 32

Gnomad AFR AF: 0.246

Gnomad AMI AF: 0.0824

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0805

Gnomad EAS AF: 0.00270

Gnomad SAS AF: 0.150

Gnomad FIN AF: 0.156

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.149

GnomAD3 exomes AF: 0.147 AC: 36676 AN: 250314 Hom.: 3246 AF XY: 0.148 AC XY: 20031 AN XY: 135340

Gnomad AFR exome AF: 0.245

Gnomad AMR exome AF: 0.0718

Gnomad ASJ exome AF: 0.0811

Gnomad EAS exome AF: 0.00153

Gnomad SAS exome AF: 0.145

Gnomad FIN exome AF: 0.165

Gnomad NFE exome AF: 0.181

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.174 AC: 254310 AN: 1460578 Hom.: 23558 Cov.: 36 AF XY: 0.173 AC XY: 125737 AN XY: 726516

Gnomad4 AFR exome AF: 0.245

Gnomad4 AMR exome AF: 0.0760

Gnomad4 ASJ exome AF: 0.0814

Gnomad4 EAS exome AF: 0.00103

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.166

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.157

GnomAD4 genome AF: 0.180 AC: 27355 AN: 152032 Hom.: 2751 Cov.: 32 AF XY: 0.175 AC XY: 13022 AN XY: 74304

Gnomad4 AFR AF: 0.246

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0805

Gnomad4 EAS AF: 0.00290

Gnomad4 SAS AF: 0.150

Gnomad4 FIN AF: 0.156

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.147

Alfa AF: 0.157 Hom.: 379

Bravo AF: 0.176

Asia WGS AF: 0.0700 AC: 242 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Jan 24, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 23% of patients studied by a panel of primary immunodeficiencies. Number of patients: 20. Only high quality variants are reported. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.4
DANN	Benign	0.47

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: rs73037453; hg19: chr19-33464225;