rs2973646

Variant names:

• chr5-44387435-A-C
• rs2973646
• NM_004465.2:c.325+923T>G

Your query was ambiguous. Multiple possible variants found:

• chr5-44387435-A-C
• chr5-44387435-A-G
• chr5-44387435-A-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+923T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.757 in 152,110 control chromosomes in the GnomAD database, including 43,823 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 0.76 (43823 hom., cov: 32)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.945
• Publications: 6 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=-0.86).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.792 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF10	NM_004465.2	c.325+923T>G		intron_variant	Intron 1 of 2	ENST00000264664.5	NP_004456.1
FGF10	XM_005248264.5	c.325+923T>G		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+923T>G		intron_variant	Intron 1 of 2	1	NM_004465.2	ENSP00000264664.4

Frequencies

GnomAD3 genomes AF: 0.757 AC: 115122 AN: 151992 Hom.: 43803 Cov.: 32

Gnomad AFR AF: 0.718

Gnomad AMI AF: 0.753

Gnomad AMR AF: 0.676

Gnomad ASJ AF: 0.805

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.774

Gnomad FIN AF: 0.769

Gnomad MID AF: 0.823

Gnomad NFE AF: 0.797

Gnomad OTH AF: 0.774

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

GnomAD4 genome AF: 0.757 AC: 115180 AN: 152110 Hom.: 43823 Cov.: 32 AF XY: 0.758 AC XY: 56385 AN XY: 74358

African (AFR) AF: 0.718 AC: 29778 AN: 41476

American (AMR) AF: 0.675 AC: 10308 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.805 AC: 2793 AN: 3470

East Asian (EAS) AF: 0.710 AC: 3656 AN: 5152

South Asian (SAS) AF: 0.775 AC: 3730 AN: 4814

European-Finnish (FIN) AF: 0.769 AC: 8154 AN: 10600

Middle Eastern (MID) AF: 0.816 AC: 240 AN: 294

European-Non Finnish (NFE) AF: 0.797 AC: 54215 AN: 68008

Other (OTH) AF: 0.767 AC: 1619 AN: 2112

Alfa AF: 0.783 Hom.: 18177

Bravo AF: 0.746

Asia WGS AF: 0.648 AC: 2252 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	13
DANN	Benign	0.71
PhyloP100		0.94
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: rs2973646; hg19: chr5-44387537;