rs2239360

Variant names:

• chr16-89783175-C-T
• rs2239360
• NM_000135.4:c.1471-73G>A

Your query was ambiguous. Multiple possible variants found:

• chr16-89783175-C-T
• chr16-89783175-C-G

Variant summary

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

The NM_000135.4(FANCA):​c.1471-73G>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 1,100,878 control chromosomes in the GnomAD database, including 99,850 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.46 (18724 hom., cov: 32)
  • Exomes 𝑓: 0.39 (81126 hom.)
• Consequence: FANCA NM_000135.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.84
• Publications: 16 publications found

Genes affected

FANCA (HGNC:3582): (FA complementation group A) 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 A. Alternative splicing results in multiple transcript variants encoding different isoforms. Mutations in this gene are the most common cause of Fanconi anemia. [provided by RefSeq, Jul 2008]

FANCA Gene-Disease associations (from GenCC):

• Fanconi anemia complementation group A

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Ambry Genetics, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen, G2P, Myriad Women’s Health
• 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=-0.93).
• BP6: Variant 16-89783175-C-T is Benign according to our data. Variant chr16-89783175-C-T is described in ClinVar as Benign. ClinVar VariationId is 1180470.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.741 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000135.4. 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
	FANCA	NM_000135.4	MANE Select	c.1471-73G>A		intron	N/A	NP_000126.2	O15360-1
	FANCA	NM_001286167.3		c.1471-73G>A		intron	N/A	NP_001273096.1	O15360-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCA	ENST00000389301.8	TSL:1 MANE Select	c.1471-73G>A		intron	N/A	ENSP00000373952.3	O15360-1
	FANCA	ENST00000567205.2	TSL:1	n.1471-73G>A		intron	N/A	ENSP00000457027.2	H3BT53
	FANCA	ENST00000564475.6	TSL:2	c.1471-73G>A		intron	N/A	ENSP00000454977.2	H3BNS0

Frequencies

GnomAD3 genomes AF: 0.463 AC: 70368 AN: 151900 Hom.: 18703 Cov.: 32

Gnomad AFR AF: 0.683

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.504

Gnomad ASJ AF: 0.269

Gnomad EAS AF: 0.762

Gnomad SAS AF: 0.599

Gnomad FIN AF: 0.408

Gnomad MID AF: 0.225

Gnomad NFE AF: 0.312

Gnomad OTH AF: 0.401

GnomAD4 exome AF: 0.391 AC: 370716 AN: 948860 Hom.: 81126 AF XY: 0.393 AC XY: 193240 AN XY: 491426

African (AFR) AF: 0.694 AC: 15945 AN: 22984

American (AMR) AF: 0.621 AC: 24432 AN: 39368

Ashkenazi Jewish (ASJ) AF: 0.268 AC: 6075 AN: 22668

East Asian (EAS) AF: 0.829 AC: 30031 AN: 36244

South Asian (SAS) AF: 0.565 AC: 41623 AN: 73618

European-Finnish (FIN) AF: 0.401 AC: 20777 AN: 51840

Middle Eastern (MID) AF: 0.327 AC: 1286 AN: 3938

European-Non Finnish (NFE) AF: 0.326 AC: 213772 AN: 655056

Other (OTH) AF: 0.389 AC: 16775 AN: 43144

GnomAD4 genome AF: 0.463 AC: 70449 AN: 152018 Hom.: 18724 Cov.: 32 AF XY: 0.475 AC XY: 35281 AN XY: 74290

African (AFR) AF: 0.683 AC: 28320 AN: 41458

American (AMR) AF: 0.505 AC: 7703 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.269 AC: 934 AN: 3470

East Asian (EAS) AF: 0.761 AC: 3934 AN: 5172

South Asian (SAS) AF: 0.598 AC: 2884 AN: 4822

European-Finnish (FIN) AF: 0.408 AC: 4316 AN: 10578

Middle Eastern (MID) AF: 0.235 AC: 69 AN: 294

European-Non Finnish (NFE) AF: 0.312 AC: 21174 AN: 67954

Other (OTH) AF: 0.406 AC: 855 AN: 2104

Alfa AF: 0.388 Hom.: 5338

Bravo AF: 0.481

Asia WGS AF: 0.672 AC: 2336 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.31
DANN	Benign	0.55
PhyloP100		-1.8
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: rs2239360; hg19: chr16-89849583; COSMIC: COSV66881248; COSMIC: COSV66881248;