5-44305272-C-T

Position:

• chr5-44305272-C-T

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.430-80G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0187 in 1,302,442 control chromosomes in the GnomAD database, including 296 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.015 (29 hom., cov: 33)
  • Exomes 𝑓: 0.019 (267 hom.)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.0760

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=-0.85).
• BP6: Variant 5-44305272-C-T is Benign according to our data. Variant chr5-44305272-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 1183828.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 = 0.0146 (2215/152032) while in subpopulation NFE AF= 0.0234 (1591/68014). AF 95% confidence interval is 0.0224. There are 29 homozygotes in gnomad4. There are 1078 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 2215 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF10	NM_004465.2	c.430-80G>A		intron_variant		ENST00000264664.5	NP_004456.1
FGF10	XM_005248264.5	c.430-80G>A		intron_variant			XP_005248321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF10	ENST00000264664.5	c.430-80G>A		intron_variant		1	NM_004465.2	ENSP00000264664	P1

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2217 AN: 151914 Hom.: 29 Cov.: 33

Gnomad AFR AF: 0.00348

Gnomad AMI AF: 0.0373

Gnomad AMR AF: 0.00580

Gnomad ASJ AF: 0.00202

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00249

Gnomad FIN AF: 0.0302

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0234

Gnomad OTH AF: 0.0100

GnomAD4 exome AF: 0.0192 AC: 22125 AN: 1150410 Hom.: 267 AF XY: 0.0188 AC XY: 11037 AN XY: 586474

Gnomad4 AFR exome AF: 0.00325

Gnomad4 AMR exome AF: 0.00460

Gnomad4 ASJ exome AF: 0.000249

Gnomad4 EAS exome AF: 0.0000793

Gnomad4 SAS exome AF: 0.00175

Gnomad4 FIN exome AF: 0.0329

Gnomad4 NFE exome AF: 0.0231

Gnomad4 OTH exome AF: 0.0147

GnomAD4 genome AF: 0.0146 AC: 2215 AN: 152032 Hom.: 29 Cov.: 33 AF XY: 0.0145 AC XY: 1078 AN XY: 74306

Gnomad4 AFR AF: 0.00347

Gnomad4 AMR AF: 0.00573

Gnomad4 ASJ AF: 0.00202

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00228

Gnomad4 FIN AF: 0.0302

Gnomad4 NFE AF: 0.0234

Gnomad4 OTH AF: 0.00993

Alfa AF: 0.0242 Hom.: 14

Bravo AF: 0.0122

Asia WGS AF: 0.00173 AC: 6 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	clinical testing	GeneDx	Apr 20, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.7
DANN	Benign	0.36

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: rs17228255; hg19: chr5-44305374;