11-22623057-G-A

Position:

• chr11-22623057-G-A

Variant summary

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

The NM_022725.4(FANCF):​c.*1629C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 205,596 control chromosomes in the GnomAD database, including 209 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.037 (170 hom., cov: 33)
  • Exomes 𝑓: 0.029 (39 hom.)
• Consequence: FANCF NM_022725.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.278

Genes affected

FANCF (HGNC:3587): (FA complementation group F) The Fanconi anemia complementation group (FANC) currently includes FANCA, FANCB, FANCC, FANCD1 (also called BRCA2), FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ (also called BRIP1), FANCL, FANCM and FANCN (also called PALB2). The previously defined group FANCH is the same as FANCA. Fanconi anemia is a genetically heterogeneous recessive disorder characterized by cytogenetic instability, hypersensitivity to DNA crosslinking agents, increased chromosomal breakage, and defective DNA repair. The members of the Fanconi anemia complementation group do not share sequence similarity; they are related by their assembly into a common nuclear protein complex. This gene encodes the protein for complementation group F. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 11-22623057-G-A is Benign according to our data. Variant chr11-22623057-G-A is described in ClinVar as [Benign]. Clinvar id is 304177.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr11-22623057-G-A is described in Lovd as [Likely_benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0763 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCF	NM_022725.4	c.*1629C>T		3_prime_UTR_variant	1/1	ENST00000327470.6	NP_073562.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FANCF	ENST00000327470.6	c.*1629C>T		3_prime_UTR_variant	1/1		NM_022725.4	ENSP00000330875	P1

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5677 AN: 151948 Hom.: 168 Cov.: 33

Gnomad AFR AF: 0.0783

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0369

Gnomad ASJ AF: 0.0107

Gnomad EAS AF: 0.0794

Gnomad SAS AF: 0.00477

Gnomad FIN AF: 0.0357

Gnomad MID AF: 0.00637

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0250

GnomAD4 exome AF: 0.0291 AC: 1558 AN: 53530 Hom.: 39 Cov.: 0 AF XY: 0.0278 AC XY: 690 AN XY: 24846

Gnomad4 AFR exome AF: 0.0691

Gnomad4 AMR exome AF: 0.0441

Gnomad4 ASJ exome AF: 0.00778

Gnomad4 EAS exome AF: 0.0912

Gnomad4 SAS exome AF: 0.00644

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0132

Gnomad4 OTH exome AF: 0.0238

GnomAD4 genome AF: 0.0375 AC: 5701 AN: 152066 Hom.: 170 Cov.: 33 AF XY: 0.0380 AC XY: 2827 AN XY: 74350

Gnomad4 AFR AF: 0.0785

Gnomad4 AMR AF: 0.0374

Gnomad4 ASJ AF: 0.0107

Gnomad4 EAS AF: 0.0796

Gnomad4 SAS AF: 0.00456

Gnomad4 FIN AF: 0.0357

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0247

Alfa AF: 0.0269 Hom.: 39

Bravo AF: 0.0400

Asia WGS AF: 0.0450 AC: 157 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fanconi anemia complementation group F Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	4.4
DANN	Benign	0.74

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: rs10500938; hg19: chr11-22644603;