rs1011814

Variant names:

• chr5-44335718-T-C
• rs1011814
• NM_004465.2:c.326-25188A>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.326-25188A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.541 in 151,858 control chromosomes in the GnomAD database, including 24,156 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 0.54 (24156 hom., cov: 32)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.07
• Publications: 23 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF10	NM_004465.2	c.326-25188A>G		intron_variant	Intron 1 of 2	ENST00000264664.5	NP_004456.1
FGF10	XM_005248264.5	c.326-25188A>G		intron_variant	Intron 2 of 3		XP_005248321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF10	ENST00000264664.5	c.326-25188A>G		intron_variant	Intron 1 of 2	1	NM_004465.2	ENSP00000264664.4

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82092 AN: 151736 Hom.: 24157 Cov.: 32

Gnomad AFR AF: 0.303

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.476

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.491

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.611

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.564

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

GnomAD4 genome AF: 0.541 AC: 82105 AN: 151858 Hom.: 24156 Cov.: 32 AF XY: 0.543 AC XY: 40275 AN XY: 74188

African (AFR) AF: 0.302 AC: 12541 AN: 41476

American (AMR) AF: 0.476 AC: 7243 AN: 15222

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2320 AN: 3464

East Asian (EAS) AF: 0.492 AC: 2545 AN: 5170

South Asian (SAS) AF: 0.602 AC: 2900 AN: 4816

European-Finnish (FIN) AF: 0.665 AC: 7016 AN: 10548

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

European-Non Finnish (NFE) AF: 0.672 AC: 45585 AN: 67848

Other (OTH) AF: 0.559 AC: 1179 AN: 2110

Alfa AF: 0.630 Hom.: 130523

Bravo AF: 0.514

Asia WGS AF: 0.467 AC: 1620 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	7.6
DANN	Benign	0.73
PhyloP100		1.1
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: rs1011814; hg19: chr5-44335820;