chr5-44305002-T-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004465.2(FGF10):ā€‹c.620A>Cā€‹(p.His207Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00172 in 1,613,888 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā˜…ā˜…).

Frequency

Genomes: š‘“ 0.0014 ( 1 hom., cov: 33)
Exomes š‘“: 0.0018 ( 4 hom. )

Consequence

FGF10
NM_004465.2 missense

Scores

1
18

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 1.34
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.009158462).
BP6
Variant 5-44305002-T-G is Benign according to our data. Variant chr5-44305002-T-G is described in ClinVar as [Likely_benign]. Clinvar id is 288912.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0014 (213/152324) while in subpopulation NFE AF= 0.00216 (147/68022). AF 95% confidence interval is 0.00188. There are 1 homozygotes in gnomad4. There are 103 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High AC in GnomAd4 at 213 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FGF10NM_004465.2 linkuse as main transcriptc.620A>C p.His207Pro missense_variant 3/3 ENST00000264664.5 NP_004456.1
FGF10XM_005248264.5 linkuse as main transcriptc.620A>C p.His207Pro missense_variant 4/4 XP_005248321.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FGF10ENST00000264664.5 linkuse as main transcriptc.620A>C p.His207Pro missense_variant 3/31 NM_004465.2 ENSP00000264664 P1

Frequencies

GnomAD3 genomes
AF:
0.00140
AC:
213
AN:
152206
Hom.:
1
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000327
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00471
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00216
Gnomad OTH
AF:
0.000478
GnomAD3 exomes
AF:
0.00161
AC:
405
AN:
251312
Hom.:
2
AF XY:
0.00158
AC XY:
215
AN XY:
135822
show subpopulations
Gnomad AFR exome
AF:
0.000246
Gnomad AMR exome
AF:
0.000174
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00263
Gnomad NFE exome
AF:
0.00290
Gnomad OTH exome
AF:
0.00131
GnomAD4 exome
AF:
0.00176
AC:
2567
AN:
1461564
Hom.:
4
Cov.:
31
AF XY:
0.00167
AC XY:
1214
AN XY:
727086
show subpopulations
Gnomad4 AFR exome
AF:
0.000179
Gnomad4 AMR exome
AF:
0.000157
Gnomad4 ASJ exome
AF:
0.0000383
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00303
Gnomad4 NFE exome
AF:
0.00209
Gnomad4 OTH exome
AF:
0.00118
GnomAD4 genome
AF:
0.00140
AC:
213
AN:
152324
Hom.:
1
Cov.:
33
AF XY:
0.00138
AC XY:
103
AN XY:
74478
show subpopulations
Gnomad4 AFR
AF:
0.000241
Gnomad4 AMR
AF:
0.000327
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00471
Gnomad4 NFE
AF:
0.00216
Gnomad4 OTH
AF:
0.000473
Alfa
AF:
0.00178
Hom.:
0
Bravo
AF:
0.00110
TwinsUK
AF:
0.00216
AC:
8
ALSPAC
AF:
0.00182
AC:
7
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.00186
AC:
16
ExAC
AF:
0.00198
AC:
241
EpiCase
AF:
0.00180
EpiControl
AF:
0.00160

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingEurofins Ntd Llc (ga)Aug 18, 2016- -
Congenital absence of salivary gland Benign:1
Benign, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJan 12, 2018This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
not provided Benign:1
Likely benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 11, 2023- -
FGF10-related disorder Benign:1
Likely benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesAug 16, 2019This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -
Congenital absence of salivary gland;C0265269:Levy-Hollister syndrome Benign:1
Likely benign, criteria provided, single submitterclinical testingFulgent Genetics, Fulgent GeneticsJul 14, 2021- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.12
BayesDel_addAF
Benign
-0.38
T
BayesDel_noAF
Benign
-0.32
CADD
Benign
16
DANN
Benign
0.64
DEOGEN2
Benign
0.40
T
Eigen
Benign
-0.34
Eigen_PC
Benign
-0.16
FATHMM_MKL
Benign
0.70
D
LIST_S2
Benign
0.58
T
M_CAP
Benign
0.017
T
MetaRNN
Benign
0.0092
T
MetaSVM
Benign
-0.93
T
MutationAssessor
Benign
0.0
N
MutationTaster
Benign
1.0
N
PrimateAI
Uncertain
0.61
T
PROVEAN
Benign
-0.24
N
REVEL
Benign
0.22
Sift
Benign
0.13
T
Sift4G
Benign
0.39
T
Polyphen
0.0
B
Vest4
0.17
MVP
0.77
MPC
1.9
ClinPred
0.0068
T
GERP RS
4.6
Varity_R
0.27
gMVP
0.78

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

LitVar

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

Other links and lift over

dbSNP: rs147715509; hg19: chr5-44305104; COSMIC: COSV52936730; API