5-44305207-C-G

Position:

• chr5-44305207-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004465.2(FGF10):​c.430-15G>C variant causes a splice polypyrimidine tract, 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 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.189

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF10	NM_004465.2	c.430-15G>C		splice_polypyrimidine_tract_variant, intron_variant		ENST00000264664.5	NP_004456.1
FGF10	XM_005248264.5	c.430-15G>C		splice_polypyrimidine_tract_variant, intron_variant			XP_005248321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF10	ENST00000264664.5	c.430-15G>C		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004465.2	ENSP00000264664	P1

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

GnomAD3 exomes AF: 0.226 AC: 56575 AN: 250338 Hom.: 8042 AF XY: 0.217 AC XY: 29332 AN XY: 135298

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 SAS exome AF: 0.193

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

Gnomad4 AFR exome AF: 0.0838

Gnomad4 AMR exome AF: 0.452

Gnomad4 ASJ exome AF: 0.162

Gnomad4 EAS exome AF: 0.191

Gnomad4 SAS exome AF: 0.190

Gnomad4 FIN exome AF: 0.208

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.199

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

Gnomad4 AFR AF: 0.0890

Gnomad4 AMR AF: 0.299

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.171

Gnomad4 SAS AF: 0.197

Gnomad4 FIN AF: 0.205

Gnomad4 NFE AF: 0.200

Gnomad4 OTH AF: 0.180

Alfa AF: 0.181 Hom.: 513

Bravo AF: 0.185

Asia WGS AF: 0.230 AC: 800 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital absence of salivary gland Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.9
DANN	Benign	0.60

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

Publications

LitVar

Other links and lift over

dbSNP: rs2290070; hg19: chr5-44305309; COSMIC: COSV52936543;