rs2284867

Variant names:

• chr2-162210931-A-T
• rs2284867
• NM_004460.5:c.1003-935T>A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004460.5(FAP):​c.1003-935T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0353 in 152,290 control chromosomes in the GnomAD database, including 474 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 0.035 (474 hom., cov: 32)
• Consequence: FAP NM_004460.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.361

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.208 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAP	NM_004460.5	c.1003-935T>A		intron_variant	Intron 11 of 25	ENST00000188790.9	NP_004451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAP	ENST00000188790.9	c.1003-935T>A		intron_variant	Intron 11 of 25	1	NM_004460.5	ENSP00000188790.4
FAP	ENST00000480838.1	n.990-935T>A		intron_variant	Intron 10 of 10	1
FAP	ENST00000443424.5	c.928-935T>A		intron_variant	Intron 10 of 24	2		ENSP00000411391.1

Frequencies

GnomAD3 genomes AF: 0.0351 AC: 5348 AN: 152172 Hom.: 460 Cov.: 32

Gnomad AFR AF: 0.00668

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.213

Gnomad ASJ AF: 0.00577

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.0119

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.0458

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

GnomAD4 genome AF: 0.0353 AC: 5381 AN: 152290 Hom.: 474 Cov.: 32 AF XY: 0.0383 AC XY: 2854 AN XY: 74468

Gnomad4 AFR AF: 0.00666

Gnomad4 AMR AF: 0.214

Gnomad4 ASJ AF: 0.00577

Gnomad4 EAS AF: 0.122

Gnomad4 SAS AF: 0.0207

Gnomad4 FIN AF: 0.0119

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.0529

Alfa AF: 0.0244 Hom.: 33

Bravo AF: 0.0532

Asia WGS AF: 0.108 AC: 374 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.55
DANN	Benign	0.47

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: rs2284867; hg19: chr2-163067441;