chr5-44362102-G-A

Variant names:

• chr5-44362102-G-A
• rs17234079
• NM_004465.2:c.325+26256C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004465.2(FGF10):​c.325+26256C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 151,528 control chromosomes in the GnomAD database, including 1,617 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1617 hom., cov: 32)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.988
• Publications: 7 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.187 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF10	NM_004465.2	c.325+26256C>T		intron_variant	Intron 1 of 2	ENST00000264664.5	NP_004456.1
FGF10	XM_005248264.5	c.325+26256C>T		intron_variant	Intron 2 of 3		XP_005248321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF10	ENST00000264664.5	c.325+26256C>T		intron_variant	Intron 1 of 2	1	NM_004465.2	ENSP00000264664.4

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19706 AN: 151410 Hom.: 1618 Cov.: 32

Gnomad AFR AF: 0.0310

Gnomad AMI AF: 0.206

Gnomad AMR AF: 0.138

Gnomad ASJ AF: 0.212

Gnomad EAS AF: 0.0648

Gnomad SAS AF: 0.197

Gnomad FIN AF: 0.153

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.179

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.130 AC: 19708 AN: 151528 Hom.: 1617 Cov.: 32 AF XY: 0.130 AC XY: 9611 AN XY: 74030

African (AFR) AF: 0.0309 AC: 1282 AN: 41434

American (AMR) AF: 0.138 AC: 2095 AN: 15182

Ashkenazi Jewish (ASJ) AF: 0.212 AC: 732 AN: 3452

East Asian (EAS) AF: 0.0650 AC: 332 AN: 5108

South Asian (SAS) AF: 0.198 AC: 952 AN: 4814

European-Finnish (FIN) AF: 0.153 AC: 1618 AN: 10542

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.179 AC: 12124 AN: 67684

Other (OTH) AF: 0.151 AC: 318 AN: 2106

Alfa AF: 0.172 Hom.: 4641

Bravo AF: 0.124

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.18
DANN	Benign	0.46
PhyloP100		-0.99
Mutation Taster		=100/0	polymorphism (auto)

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: rs17234079; hg19: chr5-44362204;