rs6706926

Variant names:

• chr2-162206669-T-G
• rs6706926
• NM_004460.5:c.1047+3283A>C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 5 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 -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 rank	MANE	Protein	UniProt
FAP	NM_004460.5	c.1047+3283A>C		intron_variant	Intron 12 of 25	ENST00000188790.9	NP_004451.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAP	ENST00000188790.9	c.1047+3283A>C		intron_variant	Intron 12 of 25	1	NM_004460.5	ENSP00000188790.4
FAP	ENST00000443424.5	c.972+3283A>C		intron_variant	Intron 11 of 24	2		ENSP00000411391.1

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

African (AFR) AF: 0.349 AC: 14491 AN: 41470

American (AMR) AF: 0.250 AC: 3829 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00692 AC: 24 AN: 3470

East Asian (EAS) AF: 0.121 AC: 630 AN: 5186

South Asian (SAS) AF: 0.0228 AC: 110 AN: 4830

European-Finnish (FIN) AF: 0.0121 AC: 128 AN: 10622

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0131 AC: 891 AN: 68012

Other (OTH) AF: 0.127 AC: 269 AN: 2112

Alfa AF: 0.0688 Hom.: 518

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
PhyloP100		-2.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs6706926; hg19: chr2-163063179;