rs2330545

Variant names:

• chr5-44339708-G-A
• rs2330545
• NM_004465.2:c.326-29178C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-44339708-G-A
• chr5-44339708-G-T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000264664.5(FGF10):​c.326-29178C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 151,868 control chromosomes in the GnomAD database, including 23,832 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 0.53 (23832 hom., cov: 31)
• Consequence: FGF10 ENST00000264664.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.31
• 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.24).
• 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: ENST00000264664.5. 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.326-29178C>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.326-29178C>T		intron	N/A	ENSP00000264664.4

Frequencies

GnomAD3 genomes AF: 0.533 AC: 80950 AN: 151750 Hom.: 23833 Cov.: 31

Gnomad AFR AF: 0.274

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.493

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.671

Gnomad OTH AF: 0.561

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

GnomAD4 genome AF: 0.533 AC: 80961 AN: 151868 Hom.: 23832 Cov.: 31 AF XY: 0.536 AC XY: 39739 AN XY: 74196

African (AFR) AF: 0.274 AC: 11351 AN: 41400

American (AMR) AF: 0.476 AC: 7243 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2325 AN: 3472

East Asian (EAS) AF: 0.494 AC: 2539 AN: 5138

South Asian (SAS) AF: 0.603 AC: 2906 AN: 4818

European-Finnish (FIN) AF: 0.665 AC: 7021 AN: 10550

Middle Eastern (MID) AF: 0.623 AC: 182 AN: 292

European-Non Finnish (NFE) AF: 0.672 AC: 45633 AN: 67956

Other (OTH) AF: 0.556 AC: 1167 AN: 2100

Alfa AF: 0.615 Hom.: 17172

Bravo AF: 0.504

Asia WGS AF: 0.466 AC: 1620 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.24
CADD	Benign	17
DANN	Benign	0.64
PhyloP100		1.3
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: rs2330545; hg19: chr5-44339810;