rs1374962

Variant names:

• chr5-44310968-A-G
• rs1374962
• NM_004465.2:c.326-438T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004465.2(FGF10):​c.326-438T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 151,864 control chromosomes in the GnomAD database, including 6,798 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 0.30 (6798 hom., cov: 32)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.99
• 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=-0.48).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.395 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF10	NM_004465.2	c.326-438T>C		intron_variant	Intron 1 of 2	ENST00000264664.5	NP_004456.1
FGF10	XM_005248264.5	c.326-438T>C		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.326-438T>C		intron_variant	Intron 1 of 2	1	NM_004465.2	ENSP00000264664.4

Frequencies

GnomAD3 genomes AF: 0.296 AC: 44854 AN: 151744 Hom.: 6795 Cov.: 32

Gnomad AFR AF: 0.247

Gnomad AMI AF: 0.329

Gnomad AMR AF: 0.403

Gnomad ASJ AF: 0.286

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.279

Gnomad FIN AF: 0.309

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.309

Gnomad OTH AF: 0.309

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

GnomAD4 genome AF: 0.296 AC: 44892 AN: 151864 Hom.: 6798 Cov.: 32 AF XY: 0.294 AC XY: 21800 AN XY: 74224

African (AFR) AF: 0.247 AC: 10247 AN: 41434

American (AMR) AF: 0.404 AC: 6134 AN: 15198

Ashkenazi Jewish (ASJ) AF: 0.286 AC: 992 AN: 3468

East Asian (EAS) AF: 0.170 AC: 877 AN: 5150

South Asian (SAS) AF: 0.279 AC: 1342 AN: 4810

European-Finnish (FIN) AF: 0.309 AC: 3268 AN: 10562

Middle Eastern (MID) AF: 0.299 AC: 88 AN: 294

European-Non Finnish (NFE) AF: 0.309 AC: 20985 AN: 67936

Other (OTH) AF: 0.314 AC: 660 AN: 2102

Alfa AF: 0.307 Hom.: 3560

Bravo AF: 0.304

Asia WGS AF: 0.274 AC: 954 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.48
CADD	Benign	15
DANN	Benign	0.66
PhyloP100		3.0
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: rs1374962; hg19: chr5-44311070;