5-44303658-T-C

Variant names:

• chr5-44303658-T-C
• rs1374961
• NM_004465.2:c.*1337A>G

Variant summary

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

The NM_004465.2(FGF10):​c.*1337A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.452 in 152,020 control chromosomes in the GnomAD database, including 17,369 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 0.45 (17369 hom., cov: 32)
  • Exomes 𝑓: 0.50 (0 hom.)
• Consequence: FGF10 NM_004465.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.447
• Publications: 9 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=-0.49).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.674 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF10	NM_004465.2	c.*1337A>G		3_prime_UTR_variant	Exon 3 of 3	ENST00000264664.5	NP_004456.1
FGF10	XM_005248264.5	c.*1337A>G		3_prime_UTR_variant	Exon 4 of 4		XP_005248321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF10	ENST00000264664.5	c.*1337A>G		3_prime_UTR_variant	Exon 3 of 3	1	NM_004465.2	ENSP00000264664.4

Frequencies

GnomAD3 genomes AF: 0.452 AC: 68611 AN: 151900 Hom.: 17326 Cov.: 32

Gnomad AFR AF: 0.681

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.516

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.512

Gnomad SAS AF: 0.400

Gnomad FIN AF: 0.324

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.426

GnomAD4 exome AF: 0.500 AC: 1 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.500 AC XY: 1 AN XY: 2

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.452 AC: 68712 AN: 152018 Hom.: 17369 Cov.: 32 AF XY: 0.450 AC XY: 33412 AN XY: 74312

African (AFR) AF: 0.681 AC: 28253 AN: 41484

American (AMR) AF: 0.517 AC: 7879 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1119 AN: 3470

East Asian (EAS) AF: 0.511 AC: 2643 AN: 5174

South Asian (SAS) AF: 0.399 AC: 1925 AN: 4824

European-Finnish (FIN) AF: 0.324 AC: 3431 AN: 10576

Middle Eastern (MID) AF: 0.378 AC: 111 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22121 AN: 67926

Other (OTH) AF: 0.432 AC: 912 AN: 2112

Alfa AF: 0.360 Hom.: 14995

Bravo AF: 0.479

Asia WGS AF: 0.525 AC: 1825 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.49
CADD	Benign	9.3
DANN	Benign	0.87
PhyloP100		0.45
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: rs1374961; hg19: chr5-44303760;