5-44304990-T-A

Position:

• chr5-44304990-T-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_004465.2(FGF10):​c.*5A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00259 in 1,613,838 control chromosomes in the GnomAD database, including 81 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (37 hom., cov: 33)
  • Exomes 𝑓: 0.0016 (44 hom.)
• Consequence: FGF10 NM_004465.2 3_prime_UTR
• Clinical Significance: Benign/Likely benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 1.81

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BP6: Variant 5-44304990-T-A is Benign according to our data. Variant chr5-44304990-T-A is described in ClinVar as [Likely_benign]. Clinvar id is 369476.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0122 (1851/152330) while in subpopulation AFR AF= 0.0413 (1715/41564). AF 95% confidence interval is 0.0396. There are 37 homozygotes in gnomad4. There are 863 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1851 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF10	NM_004465.2	c.*5A>T		3_prime_UTR_variant	3/3	ENST00000264664.5	NP_004456.1
FGF10	XM_005248264.5	c.*5A>T		3_prime_UTR_variant	4/4		XP_005248321.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF10	ENST00000264664.5	c.*5A>T		3_prime_UTR_variant	3/3	1	NM_004465.2	ENSP00000264664	P1

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1834 AN: 152212 Hom.: 33 Cov.: 33

Gnomad AFR AF: 0.0410

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00412

Gnomad ASJ AF: 0.0124

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000162

Gnomad OTH AF: 0.00860

GnomAD3 exomes AF: 0.00380 AC: 956 AN: 251346 Hom.: 20 AF XY: 0.00291 AC XY: 395 AN XY: 135836

Gnomad AFR exome AF: 0.0413

Gnomad AMR exome AF: 0.00301

Gnomad ASJ exome AF: 0.0133

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000653

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000246

Gnomad OTH exome AF: 0.00261

GnomAD4 exome AF: 0.00159 AC: 2330 AN: 1461508 Hom.: 44 Cov.: 31 AF XY: 0.00143 AC XY: 1037 AN XY: 727052

Gnomad4 AFR exome AF: 0.0439

Gnomad4 AMR exome AF: 0.00306

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000899

Gnomad4 OTH exome AF: 0.00464

GnomAD4 genome AF: 0.0122 AC: 1851 AN: 152330 Hom.: 37 Cov.: 33 AF XY: 0.0116 AC XY: 863 AN XY: 74488

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.00412

Gnomad4 ASJ AF: 0.0124

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000162

Gnomad4 OTH AF: 0.00851

Alfa AF: 0.00542 Hom.: 3

Bravo AF: 0.0134

Asia WGS AF: 0.00867 AC: 30 AN: 3476

EpiCase AF: 0.000545

EpiControl AF: 0.000178

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 12, 2021	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Congenital absence of salivary gland Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Levy-Hollister syndrome Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	5.5
DANN	Benign	0.67

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

Publications

LitVar

Other links and lift over

dbSNP: rs111763965; hg19: chr5-44305092;