rs2075302

Variant names:

• chr2-162219636-T-C
• rs2075302
• NM_004460.5:c.486+217A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_004460.5(FAP):​c.486+217A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.344 in 152,012 control chromosomes in the GnomAD database, including 10,511 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 0.34 (10511 hom., cov: 32)
• Consequence: FAP NM_004460.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73
• Publications: 14 publications found

Genes affected

FAP (HGNC:3590): (fibroblast activation protein alpha) The protein encoded by this gene is a homodimeric integral membrane gelatinase belonging to the serine protease family. It is selectively expressed in reactive stromal fibroblasts of epithelial cancers, granulation tissue of healing wounds, and malignant cells of bone and soft tissue sarcomas. This protein is thought to be involved in the control of fibroblast growth or epithelial-mesenchymal interactions during development, tissue repair, and epithelial carcinogenesis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Apr 2014]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.25).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAP	NM_004460.5	c.486+217A>G		intron_variant	Intron 7 of 25	ENST00000188790.9	NP_004451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAP	ENST00000188790.9	c.486+217A>G		intron_variant	Intron 7 of 25	1	NM_004460.5	ENSP00000188790.4

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52268 AN: 151894 Hom.: 10518 Cov.: 32

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.333

Gnomad AMR AF: 0.349

Gnomad ASJ AF: 0.328

Gnomad EAS AF: 0.152

Gnomad SAS AF: 0.266

Gnomad FIN AF: 0.438

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.360

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.344 AC: 52254 AN: 152012 Hom.: 10511 Cov.: 32 AF XY: 0.340 AC XY: 25249 AN XY: 74302

African (AFR) AF: 0.158 AC: 6538 AN: 41508

American (AMR) AF: 0.349 AC: 5324 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.328 AC: 1139 AN: 3470

East Asian (EAS) AF: 0.151 AC: 782 AN: 5162

South Asian (SAS) AF: 0.266 AC: 1283 AN: 4824

European-Finnish (FIN) AF: 0.438 AC: 4626 AN: 10560

Middle Eastern (MID) AF: 0.449 AC: 131 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31377 AN: 67904

Other (OTH) AF: 0.356 AC: 751 AN: 2108

Alfa AF: 0.423 Hom.: 21405

Bravo AF: 0.326

Asia WGS AF: 0.211 AC: 731 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Benign	0.76
PhyloP100		1.7
Mutation Taster		=99/1	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: rs2075302; hg19: chr2-163076146;