NM_004465.2:c.*4447T>C

Variant names:

• chr5-44300548-A-G
• rs1979079
• NM_004465.2:c.*4447T>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.*4447T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,216 control chromosomes in the GnomAD database, including 3,725 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 0.22 (3725 hom., cov: 32)
• Consequence: FGF10 NM_004465.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.150
• Publications: 2 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=-0.83).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF10	NM_004465.2	c.*4447T>C		3_prime_UTR_variant	Exon 3 of 3	ENST00000264664.5	NP_004456.1
FGF10	XM_005248264.5	c.*4447T>C		3_prime_UTR_variant	Exon 4 of 4		XP_005248321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF10	ENST00000264664.5	c.*4447T>C		3_prime_UTR_variant	Exon 3 of 3	1	NM_004465.2	ENSP00000264664.4

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32980 AN: 152096 Hom.: 3718 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.171

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.180

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.207

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

GnomAD4 genome AF: 0.217 AC: 33032 AN: 152216 Hom.: 3725 Cov.: 32 AF XY: 0.215 AC XY: 15962 AN XY: 74414

African (AFR) AF: 0.217 AC: 9026 AN: 41552

American (AMR) AF: 0.316 AC: 4830 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3468

East Asian (EAS) AF: 0.170 AC: 883 AN: 5180

South Asian (SAS) AF: 0.208 AC: 1004 AN: 4818

European-Finnish (FIN) AF: 0.205 AC: 2178 AN: 10616

Middle Eastern (MID) AF: 0.187 AC: 55 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13728 AN: 67998

Other (OTH) AF: 0.213 AC: 449 AN: 2112

Alfa AF: 0.205 Hom.: 1574

Bravo AF: 0.230

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.74
PhyloP100		0.15

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1979079; hg19: chr5-44300650;