rs16942969

Variant names:

• chr15-89292723-C-T
• rs16942969
• NM_001113378.2:c.2028C>T

Your query was ambiguous. Multiple possible variants found:

• chr15-89292723-C-T
• chr15-89292723-C-A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001113378.2(FANCI):​c.2028C>T​(p.Ala676Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00615 in 1,613,680 control chromosomes in the GnomAD database, including 467 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.030 (251 hom., cov: 32)
  • Exomes 𝑓: 0.0036 (216 hom.)
• Consequence: FANCI NM_001113378.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: 1.88
• Publications: 0 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 -19 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.23).
• BP6: Variant 15-89292723-C-T is Benign according to our data. Variant chr15-89292723-C-T is described in ClinVar as Benign. ClinVar VariationId is 317284.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.88 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.101 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.2028C>T	p.Ala676Ala	synonymous	Exon 21 of 38	NP_001106849.1	Q9NVI1-3
	FANCI	NM_001376911.1		c.2028C>T	p.Ala676Ala	synonymous	Exon 21 of 38	NP_001363840.1	Q9NVI1-3
	FANCI	NM_018193.3		c.2028C>T	p.Ala676Ala	synonymous	Exon 21 of 37	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.2028C>T	p.Ala676Ala	synonymous	Exon 21 of 38	ENSP00000310842.8	Q9NVI1-3
	FANCI	ENST00000674831.1		c.2028C>T	p.Ala676Ala	synonymous	Exon 21 of 39	ENSP00000502474.1	A0A6Q8PH09
	FANCI	ENST00000940814.1		c.2028C>T	p.Ala676Ala	synonymous	Exon 21 of 38	ENSP00000610873.1

Frequencies

GnomAD3 genomes AF: 0.0304 AC: 4622 AN: 152032 Hom.: 250 Cov.: 32

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0139

Gnomad ASJ AF: 0.000576

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.000897

Gnomad OTH AF: 0.0205

GnomAD2 exomes AF: 0.00835 AC: 2075 AN: 248608 AF XY: 0.00620

Gnomad AFR exome AF: 0.105

Gnomad AMR exome AF: 0.00619

Gnomad ASJ exome AF: 0.000596

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000864

Gnomad OTH exome AF: 0.00721

GnomAD4 exome AF: 0.00362 AC: 5293 AN: 1461530 Hom.: 216 Cov.: 32 AF XY: 0.00331 AC XY: 2405 AN XY: 727082

African (AFR) AF: 0.106 AC: 3563 AN: 33472

American (AMR) AF: 0.00760 AC: 340 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.000765 AC: 20 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39674

South Asian (SAS) AF: 0.000452 AC: 39 AN: 86250

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53196

Middle Eastern (MID) AF: 0.0156 AC: 90 AN: 5768

European-Non Finnish (NFE) AF: 0.000661 AC: 735 AN: 1111928

Other (OTH) AF: 0.00838 AC: 506 AN: 60388

GnomAD4 genome AF: 0.0305 AC: 4639 AN: 152150 Hom.: 251 Cov.: 32 AF XY: 0.0286 AC XY: 2130 AN XY: 74396

African (AFR) AF: 0.104 AC: 4312 AN: 41490

American (AMR) AF: 0.0139 AC: 212 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.000576 AC: 2 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10562

Middle Eastern (MID) AF: 0.0204 AC: 6 AN: 294

European-Non Finnish (NFE) AF: 0.000897 AC: 61 AN: 68008

Other (OTH) AF: 0.0208 AC: 44 AN: 2116

Alfa AF: 0.0126 Hom.: 288

Bravo AF: 0.0356

Asia WGS AF: 0.00953 AC: 33 AN: 3478

EpiCase AF: 0.00185

EpiControl AF: 0.00184

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	Fanconi anemia complementation group I (3)
-	-	2	not provided (2)
-	-	1	Fanconi anemia (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.23
CADD	Benign	10
DANN	Benign	0.65
PhyloP100		1.9
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs16942969; hg19: chr15-89835954; COSMIC: COSV104536596;