chr5-44305272-C-T

Variant names:

• chr5-44305272-C-T
• rs17228255
• NM_004465.2:c.430-80G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 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=-0.85).
• 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 VariationId 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 the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High AC in GnomAd4 at 2215 AD gene.

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.430-80G>A		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.430-80G>A		intron	N/A	ENSP00000264664.4	O15520
	FGF10	ENST00000912799.1		c.430-80G>A		intron	N/A	ENSP00000582858.1

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

African (AFR) AF: 0.00325 AC: 89 AN: 27384

American (AMR) AF: 0.00460 AC: 195 AN: 42386

Ashkenazi Jewish (ASJ) AF: 0.000249 AC: 6 AN: 24096

East Asian (EAS) AF: 0.0000793 AC: 3 AN: 37850

South Asian (SAS) AF: 0.00175 AC: 138 AN: 78772

European-Finnish (FIN) AF: 0.0329 AC: 1612 AN: 49010

Middle Eastern (MID) AF: 0.000661 AC: 3 AN: 4542

European-Non Finnish (NFE) AF: 0.0231 AC: 19339 AN: 836080

Other (OTH) AF: 0.0147 AC: 740 AN: 50290

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

African (AFR) AF: 0.00347 AC: 144 AN: 41554

American (AMR) AF: 0.00573 AC: 87 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.00202 AC: 7 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5076

South Asian (SAS) AF: 0.00228 AC: 11 AN: 4822

European-Finnish (FIN) AF: 0.0302 AC: 320 AN: 10594

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0234 AC: 1591 AN: 68014

Other (OTH) AF: 0.00993 AC: 21 AN: 2114

Alfa AF: 0.0214 Hom.: 63

Bravo AF: 0.0122

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	9.7
DANN	Benign	0.36
PhyloP100		0.076
Mutation Taster		=100/0	polymorphism

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: rs17228255; hg19: chr5-44305374;