Variant chr2-162189181-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004460.5(FAP):c.1550-9T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000552 in 1,510,168 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 3 hom., cov: 32)

Exomes 𝑓: 0.00030 ( 2 hom. )

Consequence

FAP
NM_004460.5 intron

Scores

Splicing: ADA: 0.00004213

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.114

Variant links:

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]

FAP links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.8).

BP6

Variant 2-162189181-A-G is Benign according to our data. Variant chr2-162189181-A-G is described in ClinVar as [Benign]. Clinvar id is 737646.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 3 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
FAP	NM_004460.5 link	c.1550-9T>C	intron_variant	ENST00000188790.9	NP_004451.2	Q12884-1
FAP	NM_001291807.3 link	c.1475-9T>C	intron_variant		NP_001278736.1	Q12884B4DLR2
FAP	XM_011510796.4 link	c.1520-9T>C	intron_variant		XP_011509098.1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
FAP	ENST00000188790.9 link	c.1550-9T>C	intron_variant	1	NM_004460.5	ENSP00000188790.4	Q12884-1
FAP	ENST00000422436.5 link	n.*431-9T>C	intron_variant	1		ENSP00000417028.1	H7C4D9
FAP	ENST00000443424.5 link	c.1475-9T>C	intron_variant	2		ENSP00000411391.1	B4DLR2
FAP	ENST00000497414.1 link	n.437-9T>C	intron_variant	3

Frequencies

GnomAD3 genomes

AF:

0.00283

AC:

428

AN:

151192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0100

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000463

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000443

Gnomad OTH

AF:

0.00290

GnomAD3 exomes

AF:

0.000895

AC:

177

AN:

197684

Hom.:

AF XY:

0.000584

AC XY:

AN XY:

107786

show subpopulations

Gnomad AFR exome

AF:

0.0127

Gnomad AMR exome

AF:

0.000592

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000731

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000429

Gnomad OTH exome

AF:

0.000224

GnomAD4 exome

AF:

0.000295

AC:

401

AN:

1358864

Hom.:

Cov.:

AF XY:

0.000231

AC XY:

156

AN XY:

676348

show subpopulations

Gnomad4 AFR exome

AF:

0.0106

Gnomad4 AMR exome

AF:

0.000471

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000269

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000154

Gnomad4 OTH exome

AF:

0.000751

GnomAD4 genome

AF:

0.00286

AC:

433

AN:

151304

Hom.:

Cov.:

AF XY:

0.00283

AC XY:

209

AN XY:

73902

show subpopulations

Gnomad4 AFR

AF:

0.0101

Gnomad4 AMR

AF:

0.000462

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000443

Gnomad4 OTH

AF:

0.00287

Alfa

AF:

0.00169

Hom.:

Bravo

AF:

0.00323

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Jun 06, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.37

DANN

Benign

0.77

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000042

dbscSNV1_RF

Benign

0.0060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over