chr5-44305207-C-G

Variant names:

• chr5-44305207-C-G
• rs2290070
• NM_004465.2:c.430-15G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004465.2(FGF10):​c.430-15G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.201 in 1,607,544 control chromosomes in the GnomAD database, including 35,525 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.18 (2742 hom., cov: 32)
  • Exomes 𝑓: 0.20 (32783 hom.)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.189
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 5-44305207-C-G is Benign according to our data. Variant chr5-44305207-C-G is described in ClinVar as Benign. ClinVar VariationId is 353723.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.291 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.430-15G>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.430-15G>C		intron	N/A	ENSP00000264664.4	O15520
	FGF10	ENST00000912799.1		c.430-15G>C		intron	N/A	ENSP00000582858.1

Frequencies

GnomAD3 genomes AF: 0.178 AC: 27054 AN: 152014 Hom.: 2736 Cov.: 32

Gnomad AFR AF: 0.0891

Gnomad AMI AF: 0.248

Gnomad AMR AF: 0.298

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.161

Gnomad NFE AF: 0.200

Gnomad OTH AF: 0.174

GnomAD2 exomes AF: 0.226 AC: 56575 AN: 250338 AF XY: 0.217

Gnomad AFR exome AF: 0.0863

Gnomad AMR exome AF: 0.472

Gnomad ASJ exome AF: 0.164

Gnomad EAS exome AF: 0.164

Gnomad FIN exome AF: 0.207

Gnomad NFE exome AF: 0.199

Gnomad OTH exome AF: 0.226

GnomAD4 exome AF: 0.204 AC: 296225 AN: 1455412 Hom.: 32783 Cov.: 29 AF XY: 0.202 AC XY: 146385 AN XY: 724412

African (AFR) AF: 0.0838 AC: 2795 AN: 33350

American (AMR) AF: 0.452 AC: 20193 AN: 44684

Ashkenazi Jewish (ASJ) AF: 0.162 AC: 4237 AN: 26076

East Asian (EAS) AF: 0.191 AC: 7552 AN: 39600

South Asian (SAS) AF: 0.190 AC: 16356 AN: 86114

European-Finnish (FIN) AF: 0.208 AC: 11088 AN: 53222

Middle Eastern (MID) AF: 0.140 AC: 806 AN: 5752

European-Non Finnish (NFE) AF: 0.200 AC: 221231 AN: 1106434

Other (OTH) AF: 0.199 AC: 11967 AN: 60180

GnomAD4 genome AF: 0.178 AC: 27082 AN: 152132 Hom.: 2742 Cov.: 32 AF XY: 0.177 AC XY: 13143 AN XY: 74376

African (AFR) AF: 0.0890 AC: 3699 AN: 41540

American (AMR) AF: 0.299 AC: 4560 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.172 AC: 598 AN: 3470

East Asian (EAS) AF: 0.171 AC: 880 AN: 5158

South Asian (SAS) AF: 0.197 AC: 951 AN: 4830

European-Finnish (FIN) AF: 0.205 AC: 2169 AN: 10600

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.200 AC: 13570 AN: 67952

Other (OTH) AF: 0.180 AC: 381 AN: 2114

Alfa AF: 0.181 Hom.: 513

Bravo AF: 0.185

Asia WGS AF: 0.230 AC: 800 AN: 3476

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Congenital absence of salivary gland (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.9
DANN	Benign	0.60
PhyloP100		0.19
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2290070; hg19: chr5-44305309; COSMIC: COSV52936543;