5-44328168-T-C

Variant names:

• chr5-44328168-T-C
• rs4866891
• NM_004465.2:c.326-17638A>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.326-17638A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.564 in 152,102 control chromosomes in the GnomAD database, including 25,480 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 0.56 (25480 hom., cov: 32)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 9 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=-0.61).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.666 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.326-17638A>G		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.326-17638A>G		intron	N/A	ENSP00000264664.4
	FGF10	ENST00000912799.1		c.326-17638A>G		intron	N/A	ENSP00000582858.1

Frequencies

GnomAD3 genomes AF: 0.564 AC: 85788 AN: 151984 Hom.: 25464 Cov.: 32

Gnomad AFR AF: 0.385

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.486

Gnomad ASJ AF: 0.689

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.662

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.580

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

GnomAD4 genome AF: 0.564 AC: 85831 AN: 152102 Hom.: 25480 Cov.: 32 AF XY: 0.565 AC XY: 42016 AN XY: 74348

African (AFR) AF: 0.385 AC: 15981 AN: 41482

American (AMR) AF: 0.485 AC: 7405 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.689 AC: 2391 AN: 3470

East Asian (EAS) AF: 0.493 AC: 2540 AN: 5156

South Asian (SAS) AF: 0.603 AC: 2903 AN: 4818

European-Finnish (FIN) AF: 0.662 AC: 7004 AN: 10584

Middle Eastern (MID) AF: 0.622 AC: 183 AN: 294

European-Non Finnish (NFE) AF: 0.671 AC: 45615 AN: 68008

Other (OTH) AF: 0.575 AC: 1214 AN: 2112

Alfa AF: 0.647 Hom.: 27297

Bravo AF: 0.541

Asia WGS AF: 0.480 AC: 1669 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.61
CADD	Benign	8.2
DANN	Benign	0.52
PhyloP100		0.094
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: rs4866891; hg19: chr5-44328270;