NM_000136.3:c.*1871G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000136.3(FANCC):c.*1871G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 232,466 control chromosomes in the GnomAD database, including 18,478 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.38 ( 11349 hom., cov: 32)

Exomes 𝑓: 0.41 ( 7129 hom. )

Consequence

FANCC
NM_000136.3 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.282

Publications

16 publications found

Variant links:

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]

FANCC links:

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]

AOPEP links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.548 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FANCC	NM_000136.3 link	c.*1871G>A		3_prime_UTR_variant	Exon 15 of 15	ENST00000289081.8	NP_000127.2	Q00597A0A024R9N2

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
FANCC	ENST00000289081.8 link	c.*1871G>A	3_prime_UTR_variant	Exon 15 of 15	1	NM_000136.3	ENSP00000289081.3	Q00597
FANCC	ENST00000375305.6 link	c.*1871G>A	3_prime_UTR_variant	Exon 15 of 15	1		ENSP00000364454.1	Q00597
FANCC	ENST00000696260.1 link	n.4363G>A	non_coding_transcript_exon_variant	Exon 3 of 3
AOPEP	ENST00000710812.1 link	n.410+19056C>T	intron_variant	Intron 4 of 4

Frequencies

GnomAD3 genomes

AF:

0.376

AC:

57055

AN:

151922

Hom.:

11343

Cov.:

show subpopulations

Gnomad AFR

AF:

0.237

Gnomad AMI

AF:

0.474

Gnomad AMR

AF:

0.473

Gnomad ASJ

AF:

0.303

Gnomad EAS

AF:

0.567

Gnomad SAS

AF:

0.455

Gnomad FIN

AF:

0.461

Gnomad MID

AF:

0.351

Gnomad NFE

AF:

0.407

Gnomad OTH

AF:

0.391

GnomAD4 exome

AF:

0.410

AC:

32979

AN:

80426

Hom.:

7129

Cov.:

AF XY:

0.406

AC XY:

15095

AN XY:

37210

show subpopulations

African (AFR)

AF:

0.240

AC:

919

AN:

3834

American (AMR)

AF:

0.487

AC:

1194

AN:

2454

Ashkenazi Jewish (ASJ)

AF:

0.306

AC:

1555

AN:

5074

East Asian (EAS)

AF:

0.566

AC:

6389

AN:

11286

South Asian (SAS)

AF:

0.434

AC:

307

AN:

708

European-Finnish (FIN)

AF:

0.543

AC:

AN:

Middle Eastern (MID)

AF:

0.343

AC:

170

AN:

496

European-Non Finnish (NFE)

AF:

0.399

AC:

19884

AN:

49788

Other (OTH)

AF:

0.375

AC:

2511

AN:

6694

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

980

1960

2940

3920

4900

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.375

AC:

57067

AN:

152040

Hom.:

11349

Cov.:

AF XY:

0.382

AC XY:

28393

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.237

AC:

9818

AN:

41490

American (AMR)

AF:

0.473

AC:

7229

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.303

AC:

1052

AN:

3468

East Asian (EAS)

AF:

0.566

AC:

2907

AN:

5140

South Asian (SAS)

AF:

0.455

AC:

2189

AN:

4816

European-Finnish (FIN)

AF:

0.461

AC:

4878

AN:

10584

Middle Eastern (MID)

AF:

0.347

AC:

102

AN:

294

European-Non Finnish (NFE)

AF:

0.407

AC:

27626

AN:

67946

Other (OTH)

AF:

0.395

AC:

836

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

1770

3541

5311

7082

8852

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.380

Hom.:

4591

Bravo

AF:

0.369

Asia WGS

AF:

0.480

AC:

1666

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Fanconi anemia complementation group C

Benign:1

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.88

(source)

DANN

Benign

0.46

PhyloP100

-0.28

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

NM_000136.3:c.*1871G>A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over