NM_004465.2:c.430-221A>T

Variant names:

• chr5-44305413-T-A
• rs6451758
• NM_004465.2:c.430-221A>T

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004465.2(FGF10):​c.430-221A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.217 in 152,144 control chromosomes in the GnomAD database, including 3,722 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (3722 hom., cov: 32)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.153
• Publications: 5 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 5-44305413-T-A is Benign according to our data. Variant chr5-44305413-T-A is described in ClinVar as Benign. ClinVar VariationId is 1271424.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.309 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF10	NM_004465.2	c.430-221A>T		intron_variant	Intron 2 of 2	ENST00000264664.5	NP_004456.1
FGF10	XM_005248264.5	c.430-221A>T		intron_variant	Intron 3 of 3		XP_005248321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF10	ENST00000264664.5	c.430-221A>T		intron_variant	Intron 2 of 2	1	NM_004465.2	ENSP00000264664.4

Frequencies

GnomAD3 genomes AF: 0.217 AC: 32948 AN: 152026 Hom.: 3716 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.316

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.202

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.217 AC: 32998 AN: 152144 Hom.: 3722 Cov.: 32 AF XY: 0.214 AC XY: 15941 AN XY: 74400

African (AFR) AF: 0.217 AC: 9003 AN: 41504

American (AMR) AF: 0.316 AC: 4830 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 609 AN: 3468

East Asian (EAS) AF: 0.171 AC: 883 AN: 5168

South Asian (SAS) AF: 0.208 AC: 1006 AN: 4828

European-Finnish (FIN) AF: 0.205 AC: 2169 AN: 10594

Middle Eastern (MID) AF: 0.190 AC: 56 AN: 294

European-Non Finnish (NFE) AF: 0.202 AC: 13725 AN: 67992

Other (OTH) AF: 0.212 AC: 447 AN: 2112

Alfa AF: 0.209 Hom.: 425

Bravo AF: 0.230

Asia WGS AF: 0.240 AC: 835 AN: 3472

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 08, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.18
DANN	Benign	0.33
PhyloP100		-0.15
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: rs6451758; hg19: chr5-44305515;