rs2159081

Variant names:

• chr15-89301457-A-C
• rs2159081
• NM_001113378.2:c.3006+15A>C

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.3006+15A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.39 in 1,526,138 control chromosomes in the GnomAD database, including 116,651 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.38 (11086 hom., cov: 32)
  • Exomes 𝑓: 0.39 (105565 hom.)
• Consequence: FANCI NM_001113378.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.08
• Publications: 15 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: ClinGen, Labcorp Genetics (formerly Invitae), G2P
• Fanconi anemia

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

LOC124903548 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 15-89301457-A-C is Benign according to our data. Variant chr15-89301457-A-C is described in ClinVar as Benign. ClinVar VariationId is 257487.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.39 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCI	NM_001113378.2	MANE Select	c.3006+15A>C		intron	N/A	NP_001106849.1
	FANCI	NM_001376911.1		c.3006+15A>C		intron	N/A	NP_001363840.1
	FANCI	NM_018193.3		c.2826+15A>C		intron	N/A	NP_060663.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCI	ENST00000310775.12	TSL:1 MANE Select	c.3006+15A>C		intron	N/A	ENSP00000310842.8
	FANCI	ENST00000674831.1		c.3006+15A>C		intron	N/A	ENSP00000502474.1
	FANCI	ENST00000940814.1		c.3030+15A>C		intron	N/A	ENSP00000610873.1

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57561 AN: 151882 Hom.: 11070 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.493

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.394

Gnomad OTH AF: 0.368

GnomAD2 exomes AF: 0.393 AC: 98913 AN: 251464 AF XY: 0.397

Gnomad AFR exome AF: 0.327

Gnomad AMR exome AF: 0.382

Gnomad ASJ exome AF: 0.389

Gnomad EAS exome AF: 0.382

Gnomad FIN exome AF: 0.485

Gnomad NFE exome AF: 0.389

Gnomad OTH exome AF: 0.386

GnomAD4 exome AF: 0.391 AC: 537004 AN: 1374138 Hom.: 105565 Cov.: 22 AF XY: 0.392 AC XY: 269901 AN XY: 688942

African (AFR) AF: 0.335 AC: 10648 AN: 31778

American (AMR) AF: 0.377 AC: 16808 AN: 44618

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 10041 AN: 25606

East Asian (EAS) AF: 0.355 AC: 13951 AN: 39272

South Asian (SAS) AF: 0.405 AC: 34262 AN: 84624

European-Finnish (FIN) AF: 0.479 AC: 25564 AN: 53366

Middle Eastern (MID) AF: 0.372 AC: 2088 AN: 5614

European-Non Finnish (NFE) AF: 0.389 AC: 401208 AN: 1031836

Other (OTH) AF: 0.391 AC: 22434 AN: 57424

GnomAD4 genome AF: 0.379 AC: 57607 AN: 152000 Hom.: 11086 Cov.: 32 AF XY: 0.386 AC XY: 28695 AN XY: 74284

African (AFR) AF: 0.336 AC: 13930 AN: 41464

American (AMR) AF: 0.348 AC: 5320 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1307 AN: 3470

East Asian (EAS) AF: 0.376 AC: 1939 AN: 5160

South Asian (SAS) AF: 0.397 AC: 1914 AN: 4816

European-Finnish (FIN) AF: 0.493 AC: 5198 AN: 10552

Middle Eastern (MID) AF: 0.344 AC: 101 AN: 294

European-Non Finnish (NFE) AF: 0.394 AC: 26775 AN: 67954

Other (OTH) AF: 0.365 AC: 770 AN: 2110

Alfa AF: 0.376 Hom.: 6631

Bravo AF: 0.368

Asia WGS AF: 0.367 AC: 1275 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.92
CADD	Benign	0.47
DANN	Benign	0.38
PhyloP100		-1.1
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2159081; hg19: chr15-89844688; COSMIC: COSV55522210; COSMIC: COSV55522210;