5-44375168-C-G

Variant names:

• chr5-44375168-C-G
• rs10805683
• NM_004465.2:c.325+13190G>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.325+13190G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.231 in 151,970 control chromosomes in the GnomAD database, including 4,224 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 0.23 (4224 hom., cov: 31)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0920
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 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.325+13190G>C		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.325+13190G>C		intron	N/A	ENSP00000264664.4	O15520
	FGF10	ENST00000912799.1		c.325+13190G>C		intron	N/A	ENSP00000582858.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 35039 AN: 151852 Hom.: 4199 Cov.: 31

Gnomad AFR AF: 0.241

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.292

Gnomad SAS AF: 0.227

Gnomad FIN AF: 0.231

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.217

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

GnomAD4 genome AF: 0.231 AC: 35112 AN: 151970 Hom.: 4224 Cov.: 31 AF XY: 0.231 AC XY: 17126 AN XY: 74272

African (AFR) AF: 0.241 AC: 9988 AN: 41438

American (AMR) AF: 0.321 AC: 4899 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 675 AN: 3470

East Asian (EAS) AF: 0.292 AC: 1504 AN: 5158

South Asian (SAS) AF: 0.227 AC: 1092 AN: 4818

European-Finnish (FIN) AF: 0.231 AC: 2440 AN: 10542

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13763 AN: 67954

Other (OTH) AF: 0.224 AC: 474 AN: 2112

Alfa AF: 0.116 Hom.: 181

Bravo AF: 0.240

Asia WGS AF: 0.354 AC: 1230 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.5
DANN	Benign	0.56
PhyloP100		-0.092
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: rs10805683; hg19: chr5-44375270;