rs9806604

Variant names:

• chr15-89283265-C-T
• rs9806604
• NM_001113378.2:c.1698+15C>T

Variant summary

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

The NM_001113378.2(FANCI):​c.1698+15C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 1,612,664 control chromosomes in the GnomAD database, including 133,753 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (17029 hom., cov: 32)
  • Exomes 𝑓: 0.40 (116724 hom.)
• Consequence: FANCI NM_001113378.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -0.834
• Publications: 12 publications found

Genes affected

FANCI (HGNC:25568): (FA complementation group I) 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 I. Alternative splicing results in two transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

FANCI Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group I

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), ClinGen, G2P
• 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=-0.87).
• BP6: Variant 15-89283265-C-T is Benign according to our data. Variant chr15-89283265-C-T is described in ClinVar as Benign. ClinVar VariationId is 257481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001113378.2. 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
	FANCI	NM_001113378.2	MANE Select	c.1698+15C>T		intron	N/A	NP_001106849.1	Q9NVI1-3
	FANCI	NM_001376911.1		c.1698+15C>T		intron	N/A	NP_001363840.1	Q9NVI1-3
	FANCI	NM_018193.3		c.1698+15C>T		intron	N/A	NP_060663.2	Q9NVI1-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCI	ENST00000310775.12	TSL:1 MANE Select	c.1698+15C>T		intron	N/A	ENSP00000310842.8	Q9NVI1-3
	FANCI	ENST00000674831.1		c.1698+15C>T		intron	N/A	ENSP00000502474.1	A0A6Q8PH09
	FANCI	ENST00000940814.1		c.1698+15C>T		intron	N/A	ENSP00000610873.1

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70053 AN: 151920 Hom.: 17005 Cov.: 32

Gnomad AFR AF: 0.623

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.365

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.395

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.382

Gnomad NFE AF: 0.395

Gnomad OTH AF: 0.433

GnomAD2 exomes AF: 0.412 AC: 103562 AN: 251368 AF XY: 0.410

Gnomad AFR exome AF: 0.622

Gnomad AMR exome AF: 0.402

Gnomad ASJ exome AF: 0.375

Gnomad EAS exome AF: 0.340

Gnomad FIN exome AF: 0.486

Gnomad NFE exome AF: 0.389

Gnomad OTH exome AF: 0.401

GnomAD4 exome AF: 0.397 AC: 579169 AN: 1460624 Hom.: 116724 Cov.: 34 AF XY: 0.396 AC XY: 288026 AN XY: 726666

African (AFR) AF: 0.630 AC: 21088 AN: 33448

American (AMR) AF: 0.399 AC: 17852 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.376 AC: 9812 AN: 26120

East Asian (EAS) AF: 0.326 AC: 12935 AN: 39670

South Asian (SAS) AF: 0.404 AC: 34813 AN: 86238

European-Finnish (FIN) AF: 0.479 AC: 25510 AN: 53240

Middle Eastern (MID) AF: 0.399 AC: 2301 AN: 5762

European-Non Finnish (NFE) AF: 0.387 AC: 430187 AN: 1111086

Other (OTH) AF: 0.409 AC: 24671 AN: 60342

GnomAD4 genome AF: 0.461 AC: 70117 AN: 152040 Hom.: 17029 Cov.: 32 AF XY: 0.465 AC XY: 34532 AN XY: 74316

African (AFR) AF: 0.623 AC: 25845 AN: 41482

American (AMR) AF: 0.388 AC: 5933 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.365 AC: 1265 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1750 AN: 5174

South Asian (SAS) AF: 0.396 AC: 1909 AN: 4826

European-Finnish (FIN) AF: 0.492 AC: 5187 AN: 10536

Middle Eastern (MID) AF: 0.377 AC: 110 AN: 292

European-Non Finnish (NFE) AF: 0.395 AC: 26856 AN: 67956

Other (OTH) AF: 0.430 AC: 907 AN: 2110

Alfa AF: 0.429 Hom.: 2673

Bravo AF: 0.464

Asia WGS AF: 0.378 AC: 1312 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	Fanconi anemia complementation group I (4)
-	-	2	not provided (2)
-	-	1	Fanconi anemia (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	2.1
DANN	Benign	0.62
PhyloP100		-0.83
Mutation Taster		=100/0	polymorphism (auto)

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: rs9806604; hg19: chr15-89826496; COSMIC: COSV55527271;