chr2-162172868-T-C

Variant names:

• chr2-162172868-T-C
• rs80245757
• NM_004460.5:c.2124A>G

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_004460.5(FAP):​c.2124A>G​(p.Gln708Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00303 in 1,612,514 control chromosomes in the GnomAD database, including 17 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0023 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0031 (15 hom.)
• Consequence: FAP NM_004460.5 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 3.08
• Publications: 1 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]

ENSG00000236841 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 2-162172868-T-C is Benign according to our data. Variant chr2-162172868-T-C is described in ClinVar as [Benign]. Clinvar id is 779407.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=3.08 with no splicing effect.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAP	NM_004460.5	c.2124A>G	p.Gln708Gln	synonymous_variant	Exon 25 of 26	ENST00000188790.9	NP_004451.2
FAP	NM_001291807.3	c.2049A>G	p.Gln683Gln	synonymous_variant	Exon 24 of 25		NP_001278736.1
FAP	XM_011510796.4	c.2094A>G	p.Gln698Gln	synonymous_variant	Exon 24 of 25		XP_011509098.1
LOC101929532	NR_110255.1	n.*129T>C		downstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAP	ENST00000188790.9	c.2124A>G	p.Gln708Gln	synonymous_variant	Exon 25 of 26	1	NM_004460.5	ENSP00000188790.4

Frequencies

GnomAD3 genomes AF: 0.00229 AC: 349 AN: 152114 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.000531

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000828

Gnomad FIN AF: 0.000659

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00400

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00212 AC: 532 AN: 250570 AF XY: 0.00220

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.000987

Gnomad ASJ exome AF: 0.00427

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000557

Gnomad NFE exome AF: 0.00363

Gnomad OTH exome AF: 0.00262

GnomAD4 exome AF: 0.00311 AC: 4536 AN: 1460282 Hom.: 15 Cov.: 30 AF XY: 0.00311 AC XY: 2257 AN XY: 726518

African (AFR) AF: 0.000479 AC: 16 AN: 33428

American (AMR) AF: 0.00116 AC: 52 AN: 44644

Ashkenazi Jewish (ASJ) AF: 0.00399 AC: 104 AN: 26080

East Asian (EAS) AF: 0.00 AC: 0 AN: 39672

South Asian (SAS) AF: 0.000255 AC: 22 AN: 86214

European-Finnish (FIN) AF: 0.000882 AC: 47 AN: 53304

Middle Eastern (MID) AF: 0.00313 AC: 18 AN: 5760

European-Non Finnish (NFE) AF: 0.00366 AC: 4062 AN: 1110868

Other (OTH) AF: 0.00356 AC: 215 AN: 60312

GnomAD4 genome AF: 0.00229 AC: 349 AN: 152232 Hom.: 2 Cov.: 32 AF XY: 0.00203 AC XY: 151 AN XY: 74424

African (AFR) AF: 0.000529 AC: 22 AN: 41562

American (AMR) AF: 0.00151 AC: 23 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.00404 AC: 14 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000829 AC: 4 AN: 4828

European-Finnish (FIN) AF: 0.000659 AC: 7 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00400 AC: 272 AN: 67984

Other (OTH) AF: 0.00331 AC: 7 AN: 2112

Alfa AF: 0.00316 Hom.: 0

Bravo AF: 0.00218

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00530

EpiControl AF: 0.00457

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 09, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	17
DANN	Benign	0.88
PhyloP100		3.1
Mutation Taster		=100/0	polymorphism

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: rs80245757; hg19: chr2-163029378;