5-44352242-T-C

Variant names:

• chr5-44352242-T-C
• rs1448037
• NM_004465.2:c.325+36116A>G

Variant summary

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

The NM_004465.2(FGF10):​c.325+36116A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.661 in 151,360 control chromosomes in the GnomAD database, including 33,301 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 0.66 (33301 hom., cov: 31)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.21
• Publications: 13 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=-1.03).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.689 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.325+36116A>G		intron	N/A	NP_004456.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF10	ENST00000264664.5	TSL:1 MANE Select	c.325+36116A>G		intron	N/A	ENSP00000264664.4
	FGF10	ENST00000912799.1		c.325+36116A>G		intron	N/A	ENSP00000582858.1

Frequencies

GnomAD3 genomes AF: 0.662 AC: 100055 AN: 151242 Hom.: 33302 Cov.: 31

Gnomad AFR AF: 0.646

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.527

Gnomad ASJ AF: 0.697

Gnomad EAS AF: 0.706

Gnomad SAS AF: 0.708

Gnomad FIN AF: 0.672

Gnomad MID AF: 0.703

Gnomad NFE AF: 0.691

Gnomad OTH AF: 0.653

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

GnomAD4 genome AF: 0.661 AC: 100088 AN: 151360 Hom.: 33301 Cov.: 31 AF XY: 0.661 AC XY: 48886 AN XY: 73930

African (AFR) AF: 0.646 AC: 26698 AN: 41356

American (AMR) AF: 0.526 AC: 7978 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.697 AC: 2412 AN: 3460

East Asian (EAS) AF: 0.707 AC: 3578 AN: 5064

South Asian (SAS) AF: 0.709 AC: 3404 AN: 4804

European-Finnish (FIN) AF: 0.672 AC: 7094 AN: 10560

Middle Eastern (MID) AF: 0.704 AC: 207 AN: 294

European-Non Finnish (NFE) AF: 0.691 AC: 46742 AN: 67644

Other (OTH) AF: 0.648 AC: 1362 AN: 2102

Alfa AF: 0.687 Hom.: 23710

Bravo AF: 0.648

Asia WGS AF: 0.617 AC: 2145 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.25
DANN	Benign	0.18
PhyloP100		-1.2
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: rs1448037; hg19: chr5-44352344; COSMIC: COSV52935727;