5-44365531-C-T

Variant names:

• chr5-44365531-C-T
• rs339501
• NM_004465.2:c.325+22827G>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+22827G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.94 in 151,892 control chromosomes in the GnomAD database, including 67,565 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 0.94 (67565 hom., cov: 30)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.04
• Publications: 8 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=-0.5).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 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+22827G>A		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+22827G>A		intron	N/A	ENSP00000264664.4

Frequencies

GnomAD3 genomes AF: 0.941 AC: 142770 AN: 151774 Hom.: 67548 Cov.: 30

Gnomad AFR AF: 0.840

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.924

Gnomad ASJ AF: 0.985

Gnomad EAS AF: 0.878

Gnomad SAS AF: 0.987

Gnomad FIN AF: 0.973

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.953

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

GnomAD4 genome AF: 0.940 AC: 142836 AN: 151892 Hom.: 67565 Cov.: 30 AF XY: 0.939 AC XY: 69706 AN XY: 74212

African (AFR) AF: 0.840 AC: 34791 AN: 41432

American (AMR) AF: 0.924 AC: 14044 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.985 AC: 3419 AN: 3470

East Asian (EAS) AF: 0.878 AC: 4500 AN: 5124

South Asian (SAS) AF: 0.987 AC: 4766 AN: 4828

European-Finnish (FIN) AF: 0.973 AC: 10314 AN: 10600

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67783 AN: 67918

Other (OTH) AF: 0.953 AC: 2014 AN: 2114

Alfa AF: 0.919 Hom.: 16231

Bravo AF: 0.933

Asia WGS AF: 0.890 AC: 3098 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	15
DANN	Benign	0.76
PhyloP100		1.0
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: rs339501; hg19: chr5-44365633;