rs7029888

Variant names:

• chr9-95101665-C-T
• rs7029888
• NM_000136.3:c.*42G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-95101665-C-T
• chr9-95101665-C-A
• chr9-95101665-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_000136.3(FANCC):​c.*42G>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 0.0046 in 1,611,208 control chromosomes in the GnomAD database, including 316 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.025 (171 hom., cov: 33)
  • Exomes 𝑓: 0.0025 (145 hom.)
• Consequence: FANCC NM_000136.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts U:1 B:4
• Conservation: PhyloP100: -1.58
• Publications: 1 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=-0.86).
• BP6: Variant 9-95101665-C-T is Benign according to our data. Variant chr9-95101665-C-T is described in ClinVar as Benign. ClinVar VariationId is 255272.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0849 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.*42G>A		3_prime_UTR	Exon 15 of 15	NP_000127.2	Q00597
	FANCC	NM_001243743.2		c.*42G>A		3_prime_UTR	Exon 15 of 15	NP_001230672.1	A0A024R9N2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FANCC	ENST00000289081.8	TSL:1 MANE Select	c.*42G>A		3_prime_UTR	Exon 15 of 15	ENSP00000289081.3	Q00597
	FANCC	ENST00000375305.6	TSL:1	c.*42G>A		3_prime_UTR	Exon 15 of 15	ENSP00000364454.1	Q00597
	FANCC	ENST00000863590.1		c.*42G>A		3_prime_UTR	Exon 17 of 17	ENSP00000533649.1

Frequencies

GnomAD3 genomes AF: 0.0252 AC: 3836 AN: 152172 Hom.: 170 Cov.: 33

Gnomad AFR AF: 0.0875

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.0187

GnomAD2 exomes AF: 0.00623 AC: 1548 AN: 248430 AF XY: 0.00471

Gnomad AFR exome AF: 0.0878

Gnomad AMR exome AF: 0.00302

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000978

Gnomad OTH exome AF: 0.00296

GnomAD4 exome AF: 0.00245 AC: 3576 AN: 1458918 Hom.: 145 Cov.: 31 AF XY: 0.00213 AC XY: 1544 AN XY: 725762

African (AFR) AF: 0.0898 AC: 3001 AN: 33408

American (AMR) AF: 0.00407 AC: 182 AN: 44666

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000383 AC: 33 AN: 86084

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52336

Middle Eastern (MID) AF: 0.00270 AC: 13 AN: 4806

European-Non Finnish (NFE) AF: 0.0000504 AC: 56 AN: 1111586

Other (OTH) AF: 0.00483 AC: 291 AN: 60230

GnomAD4 genome AF: 0.0252 AC: 3839 AN: 152290 Hom.: 171 Cov.: 33 AF XY: 0.0239 AC XY: 1778 AN XY: 74478

African (AFR) AF: 0.0873 AC: 3626 AN: 41548

American (AMR) AF: 0.0102 AC: 156 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10628

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000221 AC: 15 AN: 68024

Other (OTH) AF: 0.0185 AC: 39 AN: 2112

Alfa AF: 0.0103 Hom.: 20

Bravo AF: 0.0289

Asia WGS AF: 0.00577 AC: 21 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.23
DANN	Benign	0.72
PhyloP100		-1.6
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: rs7029888; hg19: chr9-97863947;