rs4647534

Variant names:

• chr9-95111675-A-G
• rs4647534
• NM_000136.3:c.1155-38T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-95111675-A-G
• chr9-95111675-A-C
• chr9-95111675-A-T

Variant summary

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

The NM_000136.3(FANCC):​c.1155-38T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,612,506 control chromosomes in the GnomAD database, including 155,817 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.48 (18407 hom., cov: 33)
  • Exomes 𝑓: 0.43 (137410 hom.)
• Consequence: FANCC NM_000136.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:6
• Conservation: PhyloP100: -0.853
• Publications: 14 publications found

Genes affected

FANCC (HGNC:3584): (FA complementation group C) 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 C. [provided by RefSeq, Jul 2008]

AOPEP (HGNC:1361): (aminopeptidase O (putative)) This gene encodes a member of the M1 zinc aminopeptidase family. The encoded protein is a zinc-dependent metallopeptidase that catalyzes the removal of an amino acid from the amino terminus of a protein or peptide. This protein may play a role in the generation of angiotensin IV. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Oct 2010]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 9-95111675-A-G is Benign according to our data. Variant chr9-95111675-A-G is described in ClinVar as Benign. ClinVar VariationId is 255273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000136.3. 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
	FANCC	NM_000136.3	MANE Select	c.1155-38T>C		intron	N/A	NP_000127.2	Q00597
	FANCC	NM_001243743.2		c.1155-38T>C		intron	N/A	NP_001230672.1	A0A024R9N2
	FANCC	NM_001243744.2		c.1155-38T>C		intron	N/A	NP_001230673.1	A0A087WW44

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	ENST00000289081.8	TSL:1 MANE Select	c.1155-38T>C		intron	N/A	ENSP00000289081.3	Q00597
	FANCC	ENST00000375305.6	TSL:1	c.1155-38T>C		intron	N/A	ENSP00000364454.1	Q00597
	FANCC	ENST00000490972.7	TSL:1	c.1155-38T>C		intron	N/A	ENSP00000479931.1	A0A087WW44

Frequencies

GnomAD3 genomes AF: 0.484 AC: 73636 AN: 152000 Hom.: 18382 Cov.: 33

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.471

Gnomad AMR AF: 0.511

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.627

Gnomad SAS AF: 0.498

Gnomad FIN AF: 0.465

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.412

Gnomad OTH AF: 0.470

GnomAD2 exomes AF: 0.473 AC: 118229 AN: 249738 AF XY: 0.464

Gnomad AFR exome AF: 0.598

Gnomad AMR exome AF: 0.568

Gnomad ASJ exome AF: 0.334

Gnomad EAS exome AF: 0.624

Gnomad FIN exome AF: 0.471

Gnomad NFE exome AF: 0.417

Gnomad OTH exome AF: 0.443

GnomAD4 exome AF: 0.429 AC: 626693 AN: 1460388 Hom.: 137410 Cov.: 35 AF XY: 0.429 AC XY: 311445 AN XY: 726558

African (AFR) AF: 0.596 AC: 19931 AN: 33444

American (AMR) AF: 0.562 AC: 25098 AN: 44698

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 8717 AN: 26124

East Asian (EAS) AF: 0.611 AC: 24262 AN: 39696

South Asian (SAS) AF: 0.466 AC: 40221 AN: 86226

European-Finnish (FIN) AF: 0.474 AC: 25223 AN: 53186

Middle Eastern (MID) AF: 0.409 AC: 2356 AN: 5764

European-Non Finnish (NFE) AF: 0.410 AC: 455043 AN: 1110904

Other (OTH) AF: 0.428 AC: 25842 AN: 60346

GnomAD4 genome AF: 0.485 AC: 73708 AN: 152118 Hom.: 18407 Cov.: 33 AF XY: 0.487 AC XY: 36215 AN XY: 74368

African (AFR) AF: 0.593 AC: 24590 AN: 41492

American (AMR) AF: 0.511 AC: 7817 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.334 AC: 1157 AN: 3468

East Asian (EAS) AF: 0.626 AC: 3235 AN: 5170

South Asian (SAS) AF: 0.498 AC: 2401 AN: 4824

European-Finnish (FIN) AF: 0.465 AC: 4914 AN: 10578

Middle Eastern (MID) AF: 0.422 AC: 124 AN: 294

European-Non Finnish (NFE) AF: 0.412 AC: 28033 AN: 67966

Other (OTH) AF: 0.476 AC: 1007 AN: 2114

Alfa AF: 0.445 Hom.: 4177

Bravo AF: 0.492

Asia WGS AF: 0.553 AC: 1922 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	Fanconi anemia complementation group C (2)
-	-	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	-0.90
CADD	Benign	0.42
DANN	Benign	0.34
PhyloP100		-0.85
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: rs4647534; hg19: chr9-97873957; COSMIC: COSV56660726; COSMIC: COSV56660726;