NM_004460.5:c.2211C>T

Variant names:

• chr2-162171051-G-A
• rs150790668
• NM_004460.5:c.2211C>T

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.2211C>T​(p.Ser737Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00214 in 1,613,066 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0022 (2 hom.)
• Consequence: FAP NM_004460.5 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.377
• Publications: 0 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=-0.71).
• BP6: Variant 2-162171051-G-A is Benign according to our data. Variant chr2-162171051-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 717148.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.377 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAP	NM_004460.5	c.2211C>T	p.Ser737Ser	synonymous_variant	Exon 26 of 26	ENST00000188790.9	NP_004451.2
FAP	NM_001291807.3	c.2136C>T	p.Ser712Ser	synonymous_variant	Exon 25 of 25		NP_001278736.1
FAP	XM_011510796.4	c.2181C>T	p.Ser727Ser	synonymous_variant	Exon 25 of 25		XP_011509098.1
LOC101929532	NR_110255.1	n.1921G>A		non_coding_transcript_exon_variant	Exon 4 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAP	ENST00000188790.9	c.2211C>T	p.Ser737Ser	synonymous_variant	Exon 26 of 26	1	NM_004460.5	ENSP00000188790.4

Frequencies

GnomAD3 genomes AF: 0.00137 AC: 208 AN: 152062 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000435

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000983

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00122

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00228

Gnomad OTH AF: 0.00335

GnomAD2 exomes AF: 0.00132 AC: 332 AN: 250884 AF XY: 0.00136

Gnomad AFR exome AF: 0.000308

Gnomad AMR exome AF: 0.000811

Gnomad ASJ exome AF: 0.000199

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.00221

Gnomad OTH exome AF: 0.00131

GnomAD4 exome AF: 0.00222 AC: 3244 AN: 1460886 Hom.: 2 Cov.: 30 AF XY: 0.00217 AC XY: 1574 AN XY: 726738

African (AFR) AF: 0.000449 AC: 15 AN: 33422

American (AMR) AF: 0.000873 AC: 39 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.0000766 AC: 2 AN: 26100

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.000162 AC: 14 AN: 86228

European-Finnish (FIN) AF: 0.00157 AC: 84 AN: 53398

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00268 AC: 2982 AN: 1111284

Other (OTH) AF: 0.00179 AC: 108 AN: 60328

GnomAD4 genome AF: 0.00137 AC: 208 AN: 152180 Hom.: 1 Cov.: 32 AF XY: 0.00132 AC XY: 98 AN XY: 74424

African (AFR) AF: 0.000434 AC: 18 AN: 41520

American (AMR) AF: 0.000982 AC: 15 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5172

South Asian (SAS) AF: 0.00 AC: 0 AN: 4814

European-Finnish (FIN) AF: 0.00122 AC: 13 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 292

European-Non Finnish (NFE) AF: 0.00228 AC: 155 AN: 68006

Other (OTH) AF: 0.00332 AC: 7 AN: 2110

Alfa AF: 0.00203 Hom.: 0

Bravo AF: 0.00124

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00262

EpiControl AF: 0.00219

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Aug 22, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely 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	-0.71
CADD	Benign	12
DANN	Benign	0.73
PhyloP100		-0.38
Mutation Taster		=99/1	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.050		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: rs150790668; hg19: chr2-163027561; COSMIC: COSV51859010; COSMIC: COSV51859010;