5-44347029-T-C

Variant names:

• chr5-44347029-T-C
• rs7708529
• NM_004465.2:c.326-36499A>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.326-36499A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.514 in 151,596 control chromosomes in the GnomAD database, including 23,077 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 0.51 (23077 hom., cov: 31)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.539
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.667 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF10	NM_004465.2	MANE Select	c.326-36499A>G		intron	N/A	NP_004456.1	O15520

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FGF10	ENST00000264664.5	TSL:1 MANE Select	c.326-36499A>G		intron	N/A	ENSP00000264664.4	O15520
	FGF10	ENST00000912799.1		c.326-36499A>G		intron	N/A	ENSP00000582858.1

Frequencies

GnomAD3 genomes AF: 0.515 AC: 77989 AN: 151478 Hom.: 23081 Cov.: 31

Gnomad AFR AF: 0.213

Gnomad AMI AF: 0.653

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.670

Gnomad EAS AF: 0.492

Gnomad SAS AF: 0.602

Gnomad FIN AF: 0.665

Gnomad MID AF: 0.619

Gnomad NFE AF: 0.672

Gnomad OTH AF: 0.546

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

GnomAD4 genome AF: 0.514 AC: 77989 AN: 151596 Hom.: 23077 Cov.: 31 AF XY: 0.517 AC XY: 38270 AN XY: 74084

African (AFR) AF: 0.213 AC: 8807 AN: 41434

American (AMR) AF: 0.461 AC: 6996 AN: 15166

Ashkenazi Jewish (ASJ) AF: 0.670 AC: 2318 AN: 3460

East Asian (EAS) AF: 0.493 AC: 2519 AN: 5108

South Asian (SAS) AF: 0.602 AC: 2899 AN: 4814

European-Finnish (FIN) AF: 0.665 AC: 7031 AN: 10574

Middle Eastern (MID) AF: 0.631 AC: 183 AN: 290

European-Non Finnish (NFE) AF: 0.672 AC: 45512 AN: 67750

Other (OTH) AF: 0.541 AC: 1130 AN: 2090

Alfa AF: 0.567 Hom.: 4072

Bravo AF: 0.483

Asia WGS AF: 0.464 AC: 1611 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.41
DANN	Benign	0.44
PhyloP100		-0.54
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: rs7708529; hg19: chr5-44347131;