rs10473352

Variant names:

• chr5-44308150-A-G
• rs10473352
• NM_004465.2:c.429+2277T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004465.2(FGF10):​c.429+2277T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.194 in 152,192 control chromosomes in the GnomAD database, including 3,048 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 0.19 (3048 hom., cov: 33)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0720
• Publications: 7 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.296 is higher than 0.05.

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.429+2277T>C		intron	N/A	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.429+2277T>C		intron	N/A	ENSP00000264664.4	O15520
	FGF10	ENST00000912799.1		c.429+2277T>C		intron	N/A	ENSP00000582858.1

Frequencies

GnomAD3 genomes AF: 0.194 AC: 29445 AN: 152072 Hom.: 3041 Cov.: 33

Gnomad AFR AF: 0.144

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.303

Gnomad ASJ AF: 0.173

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.165

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.185

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

GnomAD4 genome AF: 0.194 AC: 29478 AN: 152192 Hom.: 3048 Cov.: 33 AF XY: 0.192 AC XY: 14256 AN XY: 74394

African (AFR) AF: 0.144 AC: 5960 AN: 41532

American (AMR) AF: 0.304 AC: 4634 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.173 AC: 600 AN: 3468

East Asian (EAS) AF: 0.171 AC: 884 AN: 5178

South Asian (SAS) AF: 0.197 AC: 949 AN: 4818

European-Finnish (FIN) AF: 0.205 AC: 2171 AN: 10606

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13600 AN: 68006

Other (OTH) AF: 0.191 AC: 404 AN: 2110

Alfa AF: 0.201 Hom.: 4247

Bravo AF: 0.204

Asia WGS AF: 0.232 AC: 809 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.32
DANN	Benign	0.59
PhyloP100		-0.072
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10473352; hg19: chr5-44308252;