chr15-89295005-A-G

Variant names:

• chr15-89295005-A-G
• rs7183618
• NM_001113378.2:c.2547A>G

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001113378.2(FANCI):​c.2547A>G​(p.Lys849Lys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0497 in 1,552,292 control chromosomes in the GnomAD database, including 2,369 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.040 (214 hom., cov: 32)
  • Exomes 𝑓: 0.051 (2155 hom.)
• Consequence: FANCI NM_001113378.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.72
• Publications: 25 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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.19).
• BP6: Variant 15-89295005-A-G is Benign according to our data. Variant chr15-89295005-A-G is described in ClinVar as Benign. ClinVar VariationId is 238316.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.72 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0515 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.2547A>G	p.Lys849Lys	synonymous	Exon 24 of 38	NP_001106849.1
	FANCI	NM_001376911.1		c.2547A>G	p.Lys849Lys	synonymous	Exon 24 of 38	NP_001363840.1
	FANCI	NM_001376910.1		c.2268A>G	p.Lys756Lys	synonymous	Exon 24 of 38	NP_001363839.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCI	ENST00000310775.12	TSL:1 MANE Select	c.2547A>G	p.Lys849Lys	synonymous	Exon 24 of 38	ENSP00000310842.8
	FANCI	ENST00000674831.1		c.2547A>G	p.Lys849Lys	synonymous	Exon 24 of 39	ENSP00000502474.1
	FANCI	ENST00000696719.1		c.2547A>G	p.Lys849Lys	synonymous	Exon 25 of 39	ENSP00000512832.1

Frequencies

GnomAD3 genomes AF: 0.0403 AC: 6133 AN: 152158 Hom.: 214 Cov.: 32

Gnomad AFR AF: 0.00883

Gnomad AMI AF: 0.0504

Gnomad AMR AF: 0.0215

Gnomad ASJ AF: 0.0349

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0530

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.0507 AC: 70951 AN: 1400016 Hom.: 2155 Cov.: 31 AF XY: 0.0497 AC XY: 34286 AN XY: 690480

African (AFR) AF: 0.00687 AC: 217 AN: 31600

American (AMR) AF: 0.0160 AC: 570 AN: 35708

Ashkenazi Jewish (ASJ) AF: 0.0343 AC: 863 AN: 25182

East Asian (EAS) AF: 0.000112 AC: 4 AN: 35740

South Asian (SAS) AF: 0.0224 AC: 1774 AN: 79234

European-Finnish (FIN) AF: 0.124 AC: 6152 AN: 49564

Middle Eastern (MID) AF: 0.0182 AC: 104 AN: 5702

European-Non Finnish (NFE) AF: 0.0546 AC: 58925 AN: 1079102

Other (OTH) AF: 0.0403 AC: 2342 AN: 58184

GnomAD4 genome AF: 0.0403 AC: 6133 AN: 152276 Hom.: 214 Cov.: 32 AF XY: 0.0425 AC XY: 3166 AN XY: 74448

African (AFR) AF: 0.00881 AC: 366 AN: 41560

American (AMR) AF: 0.0214 AC: 328 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0349 AC: 121 AN: 3472

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5188

South Asian (SAS) AF: 0.0203 AC: 98 AN: 4826

European-Finnish (FIN) AF: 0.142 AC: 1504 AN: 10588

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.0530 AC: 3603 AN: 68020

Other (OTH) AF: 0.0303 AC: 64 AN: 2114

Alfa AF: 0.0407 Hom.: 157

Bravo AF: 0.0302

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Fanconi anemia Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.19
CADD	Benign	6.8
PhyloP100		1.7

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7183618; hg19: chr15-89838236;