ENST00000425676.5:n.-1C>T

Variant names:

• chr9-35079694-G-A
• rs1829148315
• NM_004629.2:c.-170C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The ENST00000425676.5(FANCG):​n.-170C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000189 in 529,726 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 31)
  • Exomes 𝑓: 0.0000019 (0 hom.)
• Consequence: FANCG ENST00000425676.5 upstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.424
• Publications: 0 publications found

Genes affected

FANCG (HGNC:3588): (FA complementation group G) 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 G. [provided by RefSeq, Jul 2008]

FANCG Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group G

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Labcorp Genetics (formerly Invitae)
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCG	NM_004629.2	c.-170C>T		5_prime_UTR_variant	Exon 1 of 14	ENST00000378643.8	NP_004620.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FANCG	ENST00000378643.8	c.-170C>T		5_prime_UTR_variant	Exon 1 of 14	1	NM_004629.2	ENSP00000367910.4

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 0.00000189 AC: 1 AN: 529726 Hom.: 0 Cov.: 6 AF XY: 0.00 AC XY: 0 AN XY: 283344

African (AFR) AF: 0.00 AC: 0 AN: 14452

American (AMR) AF: 0.00 AC: 0 AN: 26544

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16794

East Asian (EAS) AF: 0.00 AC: 0 AN: 31532

South Asian (SAS) AF: 0.0000174 AC: 1 AN: 57420

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2222

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 320268

Other (OTH) AF: 0.00 AC: 0 AN: 28880

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	5.5
DANN	Benign	0.83
PhyloP100		-0.42
PromoterAI		0.11	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs1829148315; hg19: chr9-35079691;