rs2075302

Positions:

• chr2-162219636-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000188790.9(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 ENST00000188790.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.73

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

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
FAP	NM_004460.5	c.486+217A>G		intron_variant		ENST00000188790.9	NP_004451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAP	ENST00000188790.9	c.486+217A>G		intron_variant		1	NM_004460.5	ENSP00000188790	P1
FAP	ENST00000480838.1	n.473+217A>G		intron_variant, non_coding_transcript_variant		1
FAP	ENST00000443424.5	c.411+217A>G		intron_variant		2		ENSP00000411391
FAP	ENST00000447386.5	c.423+217A>G		intron_variant		3		ENSP00000400137

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

Gnomad4 AFR AF: 0.158

Gnomad4 AMR AF: 0.349

Gnomad4 ASJ AF: 0.328

Gnomad4 EAS AF: 0.151

Gnomad4 SAS AF: 0.266

Gnomad4 FIN AF: 0.438

Gnomad4 NFE AF: 0.462

Gnomad4 OTH AF: 0.356

Alfa AF: 0.430 Hom.: 17160

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

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

LitVar

Other links and lift over

dbSNP: rs2075302; hg19: chr2-163076146;