9-35077444-T-C

Variant names:

• chr9-35077444-T-C
• rs554098
• NM_004629.2:c.511-45A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004629.2(FANCG):​c.511-45A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.765 in 1,612,430 control chromosomes in the GnomAD database, including 474,806 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.75 (43341 hom., cov: 29)
  • Exomes 𝑓: 0.77 (431465 hom.)
• Consequence: FANCG NM_004629.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.41
• Publications: 17 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BP6: Variant 9-35077444-T-C is Benign according to our data. Variant chr9-35077444-T-C is described in ClinVar as Benign. ClinVar VariationId is 259478.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

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.511-45A>G		intron	N/A	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.511-45A>G		intron	N/A	ENSP00000367910.4	O15287
	FANCG	ENST00000425676.5	TSL:1	n.308-45A>G		intron	N/A	ENSP00000412793.1	F8WC08
	FANCG	ENST00000448890.2	TSL:3	c.511-45A>G		intron	N/A	ENSP00000409607.2	O15287

Frequencies

GnomAD3 genomes AF: 0.753 AC: 114227 AN: 151754 Hom.: 43310 Cov.: 29

Gnomad AFR AF: 0.741

Gnomad AMI AF: 0.707

Gnomad AMR AF: 0.794

Gnomad ASJ AF: 0.796

Gnomad EAS AF: 0.460

Gnomad SAS AF: 0.707

Gnomad FIN AF: 0.718

Gnomad MID AF: 0.769

Gnomad NFE AF: 0.780

Gnomad OTH AF: 0.751

GnomAD2 exomes AF: 0.748 AC: 187783 AN: 251070 AF XY: 0.746

Gnomad AFR exome AF: 0.744

Gnomad AMR exome AF: 0.844

Gnomad ASJ exome AF: 0.791

Gnomad EAS exome AF: 0.452

Gnomad FIN exome AF: 0.721

Gnomad NFE exome AF: 0.778

Gnomad OTH exome AF: 0.764

GnomAD4 exome AF: 0.766 AC: 1119097 AN: 1460556 Hom.: 431465 Cov.: 37 AF XY: 0.765 AC XY: 556051 AN XY: 726678

African (AFR) AF: 0.750 AC: 25085 AN: 33448

American (AMR) AF: 0.841 AC: 37616 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.791 AC: 20667 AN: 26134

East Asian (EAS) AF: 0.491 AC: 19473 AN: 39680

South Asian (SAS) AF: 0.713 AC: 61481 AN: 86234

European-Finnish (FIN) AF: 0.719 AC: 38271 AN: 53224

Middle Eastern (MID) AF: 0.745 AC: 4296 AN: 5766

European-Non Finnish (NFE) AF: 0.780 AC: 866855 AN: 1111000

Other (OTH) AF: 0.751 AC: 45353 AN: 60352

GnomAD4 genome AF: 0.753 AC: 114310 AN: 151874 Hom.: 43341 Cov.: 29 AF XY: 0.749 AC XY: 55552 AN XY: 74212

African (AFR) AF: 0.740 AC: 30654 AN: 41406

American (AMR) AF: 0.795 AC: 12142 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.796 AC: 2761 AN: 3470

East Asian (EAS) AF: 0.461 AC: 2354 AN: 5106

South Asian (SAS) AF: 0.707 AC: 3396 AN: 4802

European-Finnish (FIN) AF: 0.718 AC: 7581 AN: 10556

Middle Eastern (MID) AF: 0.765 AC: 225 AN: 294

European-Non Finnish (NFE) AF: 0.780 AC: 52978 AN: 67942

Other (OTH) AF: 0.747 AC: 1576 AN: 2110

Alfa AF: 0.777 Hom.: 8477

Bravo AF: 0.759

Asia WGS AF: 0.583 AC: 2030 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Fanconi anemia complementation group G (2)
-	-	2	not provided (2)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	0.71
DANN	Benign	0.38
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs554098; hg19: chr9-35077441; COSMIC: COSV62719498; COSMIC: COSV62719498;