rs535188841

Variant names:

• chr9-35073858-G-A
• rs535188841
• NM_004629.2:c.*250C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004629.2(FANCG):​c.*250C>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 0.000037 in 568,278 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: FANCG NM_004629.2 3_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.380
• Publications: 1 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: ClinGen, G2P, Labcorp Genetics (formerly Invitae)
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000288699 (HGNC:):

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004629.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCG	NM_004629.2	MANE Select	c.*250C>T		3_prime_UTR	Exon 14 of 14	NP_004620.1	O15287

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCG	ENST00000378643.8	TSL:1 MANE Select	c.*250C>T		3_prime_UTR	Exon 14 of 14	ENSP00000367910.4	O15287
	FANCG	ENST00000425676.5	TSL:1	n.*1595C>T		non_coding_transcript_exon	Exon 13 of 13	ENSP00000412793.1	F8WC08
	FANCG	ENST00000425676.5	TSL:1	n.*1595C>T		3_prime_UTR	Exon 13 of 13	ENSP00000412793.1	F8WC08

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 151794 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000339

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000294

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 6 AN: 416366 Hom.: 0 Cov.: 0 AF XY: 0.0000136 AC XY: 3 AN XY: 221170

African (AFR) AF: 0.000250 AC: 3 AN: 11984

American (AMR) AF: 0.0000559 AC: 1 AN: 17904

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 13132

East Asian (EAS) AF: 0.00 AC: 0 AN: 27972

South Asian (SAS) AF: 0.0000221 AC: 1 AN: 45216

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 23974

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1814

European-Non Finnish (NFE) AF: 0.00000400 AC: 1 AN: 250226

Other (OTH) AF: 0.00 AC: 0 AN: 24144

GnomAD4 genome AF: 0.0000987 AC: 15 AN: 151912 Hom.: 0 Cov.: 32 AF XY: 0.0000943 AC XY: 7 AN XY: 74204

African (AFR) AF: 0.000314 AC: 13 AN: 41426

American (AMR) AF: 0.00 AC: 0 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10534

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000294 AC: 2 AN: 67984

Other (OTH) AF: 0.00 AC: 0 AN: 2098

Alfa AF: 0.000142 Hom.: 0

Bravo AF: 0.000136

ClinVar

ClinVar submissions as Germline

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	Fanconi anemia complementation group G (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.88
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs535188841; hg19: chr9-35073855;