NM_004465.2:c.*5A>T

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004465.2(FGF10):c.*5A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,613,838 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.012 ( 37 hom., cov: 33)

Exomes 𝑓: 0.0016 ( 44 hom. )

Consequence

FGF10
NM_004465.2 3_prime_UTR

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.81

Publications

1 publications found

Variant links:

Genes affected

FGF10 (HGNC:3666): (fibroblast growth factor 10) 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 exhibits mitogenic activity for keratinizing epidermal cells, but essentially no activity for fibroblasts, which is similar to the biological activity of FGF7. Studies of the mouse homolog of suggested that this gene is required for embryonic epidermal morphogenesis including brain development, lung morphogenesis, and initiation of lim bud formation. This gene is also implicated to be a primary factor in the process of wound healing. [provided by RefSeq, Jul 2008]

FGF10 Gene-Disease associations (from GenCC):

lacrimoauriculodentodigital syndrome 3
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
aplasia of lacrimal and salivary glands
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
LADD syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
congenital heart defects, multiple types
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
craniosynostosis
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

FGF10 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.56).

BP6

Variant 5-44304990-T-A is Benign according to our data. Variant chr5-44304990-T-A is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 369476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0122 (1851/152330) while in subpopulation AFR AF = 0.0413 (1715/41564). AF 95% confidence interval is 0.0396. There are 37 homozygotes in GnomAd4. There are 863 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.

BS2

High AC in GnomAd4 at 1851 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004465.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF10	NM_004465.2	MANE Select	c.*5A>T		3_prime_UTR	Exon 3 of 3	NP_004456.1	O15520

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF10	ENST00000264664.5	TSL:1 MANE Select	c.*5A>T		3_prime_UTR	Exon 3 of 3	ENSP00000264664.4	O15520
	FGF10	ENST00000912799.1		c.*5A>T		3_prime_UTR	Exon 4 of 4	ENSP00000582858.1

Frequencies

GnomAD3 genomes

AF:

0.0120

AC:

1834

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0410

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00412

Gnomad ASJ

AF:

0.0124

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000162

Gnomad OTH

AF:

0.00860

GnomAD2 exomes

AF:

0.00380

AC:

956

AN:

251346

AF XY:

0.00291

show subpopulations

Gnomad AFR exome

AF:

0.0413

Gnomad AMR exome

AF:

0.00301

Gnomad ASJ exome

AF:

0.0133

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000246

Gnomad OTH exome

AF:

0.00261

GnomAD4 exome

AF:

0.00159

AC:

2330

AN:

1461508

Hom.:

Cov.:

AF XY:

0.00143

AC XY:

1037

AN XY:

727052

show subpopulations

African (AFR)

AF:

0.0439

AC:

1470

AN:

33464

American (AMR)

AF:

0.00306

AC:

137

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.0119

AC:

312

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39670

South Asian (SAS)

AF:

0.000209

AC:

AN:

86246

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53412

Middle Eastern (MID)

AF:

0.00226

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000899

AC:

100

AN:

1111730

Other (OTH)

AF:

0.00464

AC:

280

AN:

60378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.481

Heterozygous variant carriers

123

246

369

492

615

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

112

168

224

280

<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:

0.0122

AC:

1851

AN:

152330

Hom.:

Cov.:

AF XY:

0.0116

AC XY:

863

AN XY:

74488

show subpopulations

African (AFR)

AF:

0.0413

AC:

1715

AN:

41564

American (AMR)

AF:

0.00412

AC:

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.0124

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.000207

AC:

AN:

4832

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000162

AC:

AN:

68038

Other (OTH)

AF:

0.00851

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

176

263

351

439

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<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:

0.00542

Hom.:

Bravo

AF:

0.0134

Asia WGS

AF:

0.00867

AC:

AN:

3476

EpiCase

AF:

0.000545

EpiControl

AF:

0.000178

ClinVar

ClinVar submissions

Significance:Benign/Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Congenital absence of salivary gland (1)

Levy-Hollister syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.56

CADD

Benign

5.5

(source)

DANN

Benign

0.67

PhyloP100

1.8

Mutation Taster

=99/1

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over