chr5-44310390-A-T

Variant names:

• chr5-44310390-A-T
• rs6881797
• NM_004465.2:c.429+37T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_004465.2(FGF10):​c.429+37T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 1,383,974 control chromosomes in the GnomAD database, including 34,826 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.22 (3841 hom., cov: 32)
  • Exomes 𝑓: 0.22 (30985 hom.)
• Consequence: FGF10 NM_004465.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.114

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 5-44310390-A-T is Benign according to our data. Variant chr5-44310390-A-T is described in ClinVar as [Benign]. Clinvar id is 1270169.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.313 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF10	NM_004465.2	c.429+37T>A		intron_variant	Intron 2 of 2	ENST00000264664.5	NP_004456.1
FGF10	XM_005248264.5	c.429+37T>A		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.429+37T>A		intron_variant	Intron 2 of 2	1	NM_004465.2	ENSP00000264664.4

Frequencies

GnomAD3 genomes AF: 0.220 AC: 33468 AN: 151980 Hom.: 3835 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.296

Gnomad AMR AF: 0.320

Gnomad ASJ AF: 0.177

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.209

Gnomad FIN AF: 0.219

Gnomad MID AF: 0.184

Gnomad NFE AF: 0.206

Gnomad OTH AF: 0.210

GnomAD2 exomes AF: 0.242 AC: 58275 AN: 240730 AF XY: 0.231

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.481

Gnomad ASJ exome AF: 0.169

Gnomad EAS exome AF: 0.163

Gnomad FIN exome AF: 0.222

Gnomad NFE exome AF: 0.205

Gnomad OTH exome AF: 0.241

GnomAD4 exome AF: 0.215 AC: 265093 AN: 1231876 Hom.: 30985 Cov.: 16 AF XY: 0.213 AC XY: 132908 AN XY: 624352

Gnomad4 AFR exome AF: 0.220 AC: 6305 AN: 28678

Gnomad4 AMR exome AF: 0.463 AC: 20161 AN: 43542

Gnomad4 ASJ exome AF: 0.168 AC: 4110 AN: 24476

Gnomad4 EAS exome AF: 0.192 AC: 7323 AN: 38158

Gnomad4 SAS exome AF: 0.203 AC: 16446 AN: 81176

Gnomad4 FIN exome AF: 0.224 AC: 11827 AN: 52784

Gnomad4 NFE exome AF: 0.206 AC: 186879 AN: 905170

Gnomad4 Remaining exome AF: 0.213 AC: 11212 AN: 52582

GnomAD4 genome AF: 0.220 AC: 33512 AN: 152098 Hom.: 3841 Cov.: 32 AF XY: 0.218 AC XY: 16211 AN XY: 74360

Gnomad4 AFR AF: 0.218 AC: 0.217652 AN: 0.217652

Gnomad4 AMR AF: 0.321 AC: 0.320562 AN: 0.320562

Gnomad4 ASJ AF: 0.177 AC: 0.177131 AN: 0.177131

Gnomad4 EAS AF: 0.171 AC: 0.171175 AN: 0.171175

Gnomad4 SAS AF: 0.209 AC: 0.208541 AN: 0.208541

Gnomad4 FIN AF: 0.219 AC: 0.219022 AN: 0.219022

Gnomad4 NFE AF: 0.206 AC: 0.205749 AN: 0.205749

Gnomad4 OTH AF: 0.215 AC: 0.215436 AN: 0.215436

Alfa AF: 0.145 Hom.: 369

Bravo AF: 0.232

Asia WGS AF: 0.240 AC: 835 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

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	-0.85
CADD	Benign	4.1
DANN	Benign	0.66
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

Publications

LitVar

Other links and lift over

dbSNP: rs6881797; hg19: chr5-44310492; COSMIC: COSV52933040;