Genetic Variant FGF8:c.*176_*187delTTTTTTTTTTTT (chr10-101770141-TAAAAAAAAAAAA-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_033163.5(FGF8):c.*176_*187delTTTTTTTTTTTT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0511 in 393,080 control chromosomes in the GnomAD database, including 465 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.044 ( 147 hom., cov: 0)

Exomes 𝑓: 0.054 ( 318 hom. )

Consequence

FGF8
NM_033163.5 3_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.86

Variant links:

Genes affected

FGF8 (HGNC:3686): (fibroblast growth factor 8) The protein encoded by this gene is a member of the fibroblast growth factor (FGF) family. FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including embryonic development, cell growth, morphogenesis, tissue repair, tumor growth and invasion. This protein is known to be a factor that supports androgen and anchorage independent growth of mammary tumor cells. Overexpression of this gene has been shown to increase tumor growth and angiogensis. The adult expression of this gene is restricted to testes and ovaries. Temporal and spatial pattern of this gene expression suggests its function as an embryonic epithelial factor. Studies of the mouse and chick homologs revealed roles in midbrain and limb development, organogenesis, embryo gastrulation and left-right axis determination. The alternative splicing of this gene results in four transcript variants. [provided by RefSeq, Jul 2008]

FGF8 links:

LOC105378457 (HGNC:):

LOC105378457 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 10-101770141-TAAAAAAAAAAAA-T is Benign according to our data. Variant chr10-101770141-TAAAAAAAAAAAA-T is described in ClinVar as [Benign]. Clinvar id is 1269222.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF8	NM_033163.5 link	c.176_187delTTTTTTTTTTTT		3_prime_UTR_variant	Exon 6 of 6	ENST00000320185.7	NP_149353.1	P55075-4A1A515

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF8	ENST00000320185 link	c.176_187delTTTTTTTTTTTT		3_prime_UTR_variant	Exon 6 of 6	1	NM_033163.5	ENSP00000321797.2		P55075-4

Frequencies

GnomAD3 genomes

AF:

0.0438

AC:

5288

AN:

120832

Hom.:

146

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0138

Gnomad AMI

AF:

0.278

Gnomad AMR

AF:

0.0501

Gnomad ASJ

AF:

0.0162

Gnomad EAS

AF:

0.000708

Gnomad SAS

AF:

0.0168

Gnomad FIN

AF:

0.0607

Gnomad MID

AF:

0.0123

Gnomad NFE

AF:

0.0605

Gnomad OTH

AF:

0.0375

GnomAD4 exome

AF:

0.0544

AC:

14807

AN:

272266

Hom.:

318

AF XY:

0.0535

AC XY:

7473

AN XY:

139806

show subpopulations

Gnomad4 AFR exome

AF:

0.0104

AC:

AN:

7506

Gnomad4 AMR exome

AF:

0.0481

AC:

471

AN:

9790

Gnomad4 ASJ exome

AF:

0.0188

AC:

171

AN:

9076

Gnomad4 EAS exome

AF:

0.0000923

AC:

AN:

21674

Gnomad4 SAS exome

AF:

0.0291

AC:

441

AN:

15132

Gnomad4 FIN exome

AF:

0.0451

AC:

888

AN:

19700

Gnomad4 NFE exome

AF:

0.0700

AC:

12007

AN:

171496

Gnomad4 Remaining exome

AF:

0.0442

AC:

736

AN:

16644

Heterozygous variant carriers

565

1129

1694

2258

2823

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Exome Het

Exome Hom

Variant carriers

172

258

344

430

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0438

AC:

5291

AN:

120814

Hom.:

147

Cov.:

AF XY:

0.0438

AC XY:

2508

AN XY:

57224

show subpopulations

Gnomad4 AFR

AF:

0.0138

AC:

0.0137606

AN:

0.0137606

Gnomad4 AMR

AF:

0.0504

AC:

0.0504458

AN:

0.0504458

Gnomad4 ASJ

AF:

0.0162

AC:

0.0162144

AN:

0.0162144

Gnomad4 EAS

AF:

0.000711

AC:

0.000711238

AN:

0.000711238

Gnomad4 SAS

AF:

0.0170

AC:

0.0169628

AN:

0.0169628

Gnomad4 FIN

AF:

0.0607

AC:

0.0607069

AN:

0.0607069

Gnomad4 NFE

AF:

0.0605

AC:

0.0604763

AN:

0.0604763

Gnomad4 OTH

AF:

0.0373

AC:

0.0373045

AN:

0.0373045

Heterozygous variant carriers

200

400

599

799

999

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Genome Het

Genome Hom

Variant carriers

120

180

240

300

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0227

Hom.:

142

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Sep 14, 2019

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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