rs16942918

Variant names:

• chr15-89260880-G-A
• rs16942918
• NM_001113378.2:c.288+37G>A

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.288+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.401 in 1,606,636 control chromosomes in the GnomAD database, including 133,307 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17674 hom., cov: 31)
  • Exomes 𝑓: 0.39 (115633 hom.)
• Consequence: FANCI NM_001113378.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -0.236
• Publications: 14 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-89260880-G-A is Benign according to our data. Variant chr15-89260880-G-A is described in ClinVar as Benign. ClinVar VariationId is 257486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.645 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.288+37G>A		intron	N/A	NP_001106849.1
	FANCI	NM_001376911.1		c.288+37G>A		intron	N/A	NP_001363840.1
	FANCI	NM_018193.3		c.288+37G>A		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.288+37G>A		intron	N/A	ENSP00000310842.8
	FANCI	ENST00000567996.5	TSL:1	c.288+37G>A		intron	N/A	ENSP00000458024.1
	FANCI	ENST00000674831.1		c.288+37G>A		intron	N/A	ENSP00000502474.1

Frequencies

GnomAD3 genomes AF: 0.468 AC: 70962 AN: 151776 Hom.: 17647 Cov.: 31

Gnomad AFR AF: 0.651

Gnomad AMI AF: 0.389

Gnomad AMR AF: 0.389

Gnomad ASJ AF: 0.377

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.382

Gnomad FIN AF: 0.492

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.393

Gnomad OTH AF: 0.435

GnomAD2 exomes AF: 0.411 AC: 103140 AN: 250888 AF XY: 0.408

Gnomad AFR exome AF: 0.650

Gnomad AMR exome AF: 0.401

Gnomad ASJ exome AF: 0.390

Gnomad EAS exome AF: 0.339

Gnomad FIN exome AF: 0.484

Gnomad NFE exome AF: 0.386

Gnomad OTH exome AF: 0.398

GnomAD4 exome AF: 0.394 AC: 573701 AN: 1454742 Hom.: 115633 Cov.: 34 AF XY: 0.394 AC XY: 285051 AN XY: 723768

African (AFR) AF: 0.657 AC: 21938 AN: 33368

American (AMR) AF: 0.398 AC: 17754 AN: 44584

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 10159 AN: 25960

East Asian (EAS) AF: 0.324 AC: 12767 AN: 39352

South Asian (SAS) AF: 0.391 AC: 33602 AN: 85958

European-Finnish (FIN) AF: 0.477 AC: 25218 AN: 52834

Middle Eastern (MID) AF: 0.399 AC: 2283 AN: 5720

European-Non Finnish (NFE) AF: 0.384 AC: 425431 AN: 1106966

Other (OTH) AF: 0.409 AC: 24549 AN: 60000

GnomAD4 genome AF: 0.468 AC: 71030 AN: 151894 Hom.: 17674 Cov.: 31 AF XY: 0.470 AC XY: 34899 AN XY: 74226

African (AFR) AF: 0.651 AC: 26978 AN: 41428

American (AMR) AF: 0.389 AC: 5938 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.377 AC: 1308 AN: 3468

East Asian (EAS) AF: 0.338 AC: 1743 AN: 5160

South Asian (SAS) AF: 0.384 AC: 1851 AN: 4826

European-Finnish (FIN) AF: 0.492 AC: 5172 AN: 10518

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.393 AC: 26665 AN: 67904

Other (OTH) AF: 0.431 AC: 909 AN: 2108

Alfa AF: 0.413 Hom.: 35528

Bravo AF: 0.472

Asia WGS AF: 0.370 AC: 1287 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.21
DANN	Benign	0.38
PhyloP100		-0.24
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: rs16942918; hg19: chr15-89804111; COSMIC: COSV55522146; COSMIC: COSV55522146;