dbSNP rs10512844: FGF10:c.326-28127G>A (chr5-44338657-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004465.2(FGF10):c.326-28127G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.308 in 152,006 control chromosomes in the GnomAD database, including 7,354 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.31 ( 7354 hom., cov: 33)

Consequence

FGF10
NM_004465.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.119

Publications

8 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.72).

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF10	NM_004465.2 link	c.326-28127G>A		intron_variant	Intron 1 of 2	ENST00000264664.5	NP_004456.1	O15520A0A7U3JW18
FGF10	XM_005248264.5 link	c.326-28127G>A		intron_variant	Intron 2 of 3		XP_005248321.1	O15520A0A7U3JW18

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF10	ENST00000264664.5 link	c.326-28127G>A		intron_variant	Intron 1 of 2	1	NM_004465.2	ENSP00000264664.4		O15520

Frequencies

GnomAD3 genomes

AF:

0.308

AC:

46809

AN:

151888

Hom.:

7336

Cov.:

show subpopulations

Gnomad AFR

AF:

0.293

Gnomad AMI

AF:

0.328

Gnomad AMR

AF:

0.408

Gnomad ASJ

AF:

0.304

Gnomad EAS

AF:

0.178

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.305

Gnomad MID

AF:

0.294

Gnomad NFE

AF:

0.308

Gnomad OTH

AF:

0.319

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.308

AC:

46881

AN:

152006

Hom.:

7354

Cov.:

AF XY:

0.306

AC XY:

22727

AN XY:

74304

show subpopulations

African (AFR)

AF:

0.293

AC:

12163

AN:

41472

American (AMR)

AF:

0.408

AC:

6221

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.304

AC:

1054

AN:

3468

East Asian (EAS)

AF:

0.178

AC:

919

AN:

5176

South Asian (SAS)

AF:

0.279

AC:

1346

AN:

4820

European-Finnish (FIN)

AF:

0.305

AC:

3218

AN:

10558

Middle Eastern (MID)

AF:

0.293

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.307

AC:

20889

AN:

67938

Other (OTH)

AF:

0.324

AC:

686

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1684

3368

5051

6735

8419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

458

916

1374

1832

2290

<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:

0.320

Hom.:

2574

Bravo

AF:

0.318

Asia WGS

AF:

0.292

AC:

1017

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.72

CADD

Benign

7.1

(source)

DANN

Benign

0.44

PhyloP100

0.12

Mutation Taster

=100/0

polymorphism (auto)

(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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over