11-22623347-A-AT

Position:

• chr11-22623347-A-AT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_022725.4(FANCF):​c.*1338_*1339insA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.96 (70353 hom., cov: 0)
  • Exomes 𝑓: 0.98 (22106 hom.)
• Consequence: FANCF NM_022725.4 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:2
• Conservation: PhyloP100: -0.574

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FANCF	NM_022725.4	c.*1338_*1339insA		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.*1338_*1339insA		3_prime_UTR_variant	1/1		NM_022725.4	ENSP00000330875	P1

Frequencies

GnomAD3 genomes AF: 0.961 AC: 146006 AN: 151896 Hom.: 70322 Cov.: 0

Gnomad AFR AF: 0.889

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.965

Gnomad ASJ AF: 0.997

Gnomad EAS AF: 0.925

Gnomad SAS AF: 0.996

Gnomad FIN AF: 0.980

Gnomad MID AF: 0.991

Gnomad NFE AF: 0.999

Gnomad OTH AF: 0.971

GnomAD4 exome AF: 0.975 AC: 45264 AN: 46424 Hom.: 22106 Cov.: 0 AF XY: 0.977 AC XY: 20850 AN XY: 21348

Gnomad4 AFR exome AF: 0.891

Gnomad4 AMR exome AF: 0.945

Gnomad4 ASJ exome AF: 0.999

Gnomad4 EAS exome AF: 0.902

Gnomad4 SAS exome AF: 0.991

Gnomad4 FIN exome AF: 0.967

Gnomad4 NFE exome AF: 0.998

Gnomad4 OTH exome AF: 0.979

GnomAD4 genome AF: 0.961 AC: 146093 AN: 152010 Hom.: 70353 Cov.: 0 AF XY: 0.961 AC XY: 71409 AN XY: 74316

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.965

Gnomad4 ASJ AF: 0.997

Gnomad4 EAS AF: 0.925

Gnomad4 SAS AF: 0.996

Gnomad4 FIN AF: 0.980

Gnomad4 NFE AF: 0.999

Gnomad4 OTH AF: 0.971

Alfa AF: 0.991 Hom.: 2232

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Fanconi anemia Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Computational scores

Source: dbNSFP v4.3

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: rs45554234; hg19: chr11-22644893;