chr5-44376958-G-A

Variant names:

• chr5-44376958-G-A
• rs1384449
• NM_004465.2:c.325+11400C>T

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+11400C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.755 in 152,066 control chromosomes in the GnomAD database, including 43,604 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 0.76 (43604 hom., cov: 31)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 11 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.792 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF10	NM_004465.2	MANE Select	c.325+11400C>T		intron	N/A	NP_004456.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF10	ENST00000264664.5	TSL:1 MANE Select	c.325+11400C>T		intron	N/A	ENSP00000264664.4
	FGF10	ENST00000912799.1		c.325+11400C>T		intron	N/A	ENSP00000582858.1

Frequencies

GnomAD3 genomes AF: 0.756 AC: 114829 AN: 151952 Hom.: 43589 Cov.: 31

Gnomad AFR AF: 0.711

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.710

Gnomad SAS AF: 0.775

Gnomad FIN AF: 0.770

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.773

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

GnomAD4 genome AF: 0.755 AC: 114876 AN: 152066 Hom.: 43604 Cov.: 31 AF XY: 0.756 AC XY: 56246 AN XY: 74354

African (AFR) AF: 0.711 AC: 29495 AN: 41474

American (AMR) AF: 0.675 AC: 10302 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.804 AC: 2787 AN: 3468

East Asian (EAS) AF: 0.710 AC: 3665 AN: 5160

South Asian (SAS) AF: 0.775 AC: 3739 AN: 4822

European-Finnish (FIN) AF: 0.770 AC: 8145 AN: 10574

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54200 AN: 67992

Other (OTH) AF: 0.767 AC: 1616 AN: 2106

Alfa AF: 0.779 Hom.: 41794

Bravo AF: 0.744

Asia WGS AF: 0.643 AC: 2238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.88
DANN	Benign	0.91
PhyloP100		-0.16
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: rs1384449; hg19: chr5-44377060;