5-44384081-C-T

Variant names:

• chr5-44384081-C-T
• rs2973644
• NM_004465.2:c.325+4277G>A

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+4277G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.742 in 151,952 control chromosomes in the GnomAD database, including 42,118 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 0.74 (42118 hom., cov: 32)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.718
• Publications: 12 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=-0.98).
• 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF10	NM_004465.2	MANE Select	c.325+4277G>A		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+4277G>A		intron	N/A	ENSP00000264664.4
	FGF10	ENST00000912799.1		c.325+4277G>A		intron	N/A	ENSP00000582858.1

Frequencies

GnomAD3 genomes AF: 0.742 AC: 112668 AN: 151834 Hom.: 42107 Cov.: 32

Gnomad AFR AF: 0.664

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.669

Gnomad ASJ AF: 0.803

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.773

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.798

Gnomad OTH AF: 0.761

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

GnomAD4 genome AF: 0.742 AC: 112712 AN: 151952 Hom.: 42118 Cov.: 32 AF XY: 0.744 AC XY: 55243 AN XY: 74268

African (AFR) AF: 0.663 AC: 27508 AN: 41462

American (AMR) AF: 0.669 AC: 10210 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.803 AC: 2788 AN: 3470

East Asian (EAS) AF: 0.709 AC: 3661 AN: 5160

South Asian (SAS) AF: 0.774 AC: 3737 AN: 4828

European-Finnish (FIN) AF: 0.769 AC: 8127 AN: 10562

Middle Eastern (MID) AF: 0.806 AC: 237 AN: 294

European-Non Finnish (NFE) AF: 0.798 AC: 54168 AN: 67884

Other (OTH) AF: 0.754 AC: 1589 AN: 2108

Alfa AF: 0.787 Hom.: 35431

Bravo AF: 0.729

Asia WGS AF: 0.640 AC: 2218 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.24
DANN	Benign	0.79
PhyloP100		-0.72
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: rs2973644; hg19: chr5-44384183;