5-44310147-G-A

Position:

• chr5-44310147-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004465.2(FGF10):​c.429+280C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0217 in 152,124 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency: Genomes: 𝑓 0.022 (54 hom., cov: 32)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.39

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=-0.68).
• BP6: Variant 5-44310147-G-A is Benign according to our data. Variant chr5-44310147-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1182654.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0217 (3298/152124) while in subpopulation NFE AF= 0.0296 (2015/67990). AF 95% confidence interval is 0.0286. There are 54 homozygotes in gnomad4. There are 1573 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3298 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF10	NM_004465.2	c.429+280C>T		intron_variant		ENST00000264664.5
FGF10	XM_005248264.5	c.429+280C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF10	ENST00000264664.5	c.429+280C>T		intron_variant		1	NM_004465.2	P1

Frequencies

GnomAD3 genomes AF: 0.0217 AC: 3298 AN: 152006 Hom.: 54 Cov.: 32

Gnomad AFR AF: 0.00493

Gnomad AMI AF: 0.138

Gnomad AMR AF: 0.0199

Gnomad ASJ AF: 0.0202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0122

Gnomad FIN AF: 0.0456

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0296

Gnomad OTH AF: 0.0172

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

GnomAD4 genome AF: 0.0217 AC: 3298 AN: 152124 Hom.: 54 Cov.: 32 AF XY: 0.0212 AC XY: 1573 AN XY: 74344

Gnomad4 AFR AF: 0.00492

Gnomad4 AMR AF: 0.0199

Gnomad4 ASJ AF: 0.0202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0125

Gnomad4 FIN AF: 0.0456

Gnomad4 NFE AF: 0.0296

Gnomad4 OTH AF: 0.0166

Alfa AF: 0.0274 Hom.: 11

Bravo AF: 0.0183

Asia WGS AF: 0.00404 AC: 14 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Feb 11, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	13
DANN	Benign	0.71

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

Publications

LitVar

Other links and lift over

dbSNP: rs17228123; hg19: chr5-44310249;