5-44389924-T-C

Variant names:

• chr5-44389924-T-C
• rs2973647
• ENST00000502457.1:n.182+1011T>C

Variant summary

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

The ENST00000502457.1(FGF10-AS1):​n.182+1011T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.969 in 151,766 control chromosomes in the GnomAD database, including 71,380 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 0.97 (71380 hom., cov: 28)
• Consequence: FGF10-AS1 ENST00000502457.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.104
• Publications: 1 publications found

Genes affected

FGF10-AS1 (HGNC:49382): (FGF10 antisense RNA 1)

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=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.992 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF10-AS1	NR_108034.1	n.182+1011T>C		intron_variant	Intron 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF10-AS1	ENST00000502457.1	n.182+1011T>C		intron_variant	Intron 1 of 2	1
FGF10	ENST00000513107.1	c.-1151A>G		upstream_gene_variant		4		ENSP00000426406.1

Frequencies

GnomAD3 genomes AF: 0.969 AC: 146962 AN: 151648 Hom.: 71332 Cov.: 28

Gnomad AFR AF: 0.937

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.934

Gnomad ASJ AF: 0.999

Gnomad EAS AF: 0.885

Gnomad SAS AF: 0.989

Gnomad FIN AF: 0.977

Gnomad MID AF: 0.997

Gnomad NFE AF: 0.998

Gnomad OTH AF: 0.972

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

GnomAD4 genome AF: 0.969 AC: 147069 AN: 151766 Hom.: 71380 Cov.: 28 AF XY: 0.967 AC XY: 71674 AN XY: 74156

African (AFR) AF: 0.937 AC: 38727 AN: 41336

American (AMR) AF: 0.934 AC: 14223 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.999 AC: 3468 AN: 3470

East Asian (EAS) AF: 0.885 AC: 4522 AN: 5110

South Asian (SAS) AF: 0.989 AC: 4732 AN: 4786

European-Finnish (FIN) AF: 0.977 AC: 10304 AN: 10550

Middle Eastern (MID) AF: 0.997 AC: 293 AN: 294

European-Non Finnish (NFE) AF: 0.998 AC: 67847 AN: 67972

Other (OTH) AF: 0.971 AC: 2041 AN: 2102

Alfa AF: 0.961 Hom.: 20540

Bravo AF: 0.965

Asia WGS AF: 0.906 AC: 3152 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	2.3
DANN	Benign	0.65
PhyloP100		-0.10
PromoterAI		-0.034	Neutral

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2973647; hg19: chr5-44390026;