rs6706926

Positions:

• chr2-162206669-T-G

Variant summary

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

The NM_004460.5(FAP):​c.1047+3283A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 152,196 control chromosomes in the GnomAD database, including 3,138 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 0.13 (3138 hom., cov: 32)
• Consequence: FAP NM_004460.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.84

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=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.345 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FAP	NM_004460.5	c.1047+3283A>C		intron_variant		ENST00000188790.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FAP	ENST00000188790.9	c.1047+3283A>C		intron_variant		1	NM_004460.5	P1
FAP	ENST00000443424.5	c.972+3283A>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.133 AC: 20261 AN: 152078 Hom.: 3089 Cov.: 32

Gnomad AFR AF: 0.348

Gnomad AMI AF: 0.00987

Gnomad AMR AF: 0.249

Gnomad ASJ AF: 0.00692

Gnomad EAS AF: 0.122

Gnomad SAS AF: 0.0228

Gnomad FIN AF: 0.0121

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.121

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

GnomAD4 genome AF: 0.134 AC: 20384 AN: 152196 Hom.: 3138 Cov.: 32 AF XY: 0.135 AC XY: 10023 AN XY: 74436

Gnomad4 AFR AF: 0.349

Gnomad4 AMR AF: 0.250

Gnomad4 ASJ AF: 0.00692

Gnomad4 EAS AF: 0.121

Gnomad4 SAS AF: 0.0228

Gnomad4 FIN AF: 0.0121

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.127

Alfa AF: 0.0629 Hom.: 257

Bravo AF: 0.166

Asia WGS AF: 0.131 AC: 455 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.032
DANN	Benign	0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs6706926; hg19: chr2-163063179;