15-49424512-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_002009.4(FGF7):c.215G>A(p.Arg72Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,988 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FGF7
NM_002009.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.45

Publications

4 publications found

Variant links:

Genes affected

FGF7 (HGNC:3685): (fibroblast growth factor 7) 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 is a potent epithelial cell-specific growth factor, whose mitogenic activity is predominantly exhibited in keratinocytes but not in fibroblasts and endothelial cells. Studies of mouse and rat homologs of this gene implicated roles in morphogenesis of epithelium, reepithelialization of wounds, hair development and early lung organogenesis. [provided by RefSeq, Jul 2008]

FGF7 links:

FAM227B (HGNC:26543): (family with sequence similarity 227 member B)

FAM227B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF7	NM_002009.4 link	c.215G>A	p.Arg72Gln	missense_variant	Exon 2 of 4	ENST00000267843.9	NP_002000.1	P21781-1A0A7U3JVY2
FAM227B	NM_152647.3 link	c.1013-53113C>T		intron_variant	Intron 11 of 15	ENST00000299338.11	NP_689860.2	Q96M60-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF7	ENST00000267843.9 link	c.215G>A	p.Arg72Gln	missense_variant	Exon 2 of 4	1	NM_002009.4	ENSP00000267843.4		P21781-1
FAM227B	ENST00000299338.11 link	c.1013-53113C>T		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6		Q96M60-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00

AC:

AN:

250136

AF XY:

0.00

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460988

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726786

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33424

American (AMR)

AF:

0.00

AC:

AN:

44694

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26106

East Asian (EAS)

AF:

0.00

AC:

AN:

39666

South Asian (SAS)

AF:

0.00

AC:

AN:

86190

European-Finnish (FIN)

AF:

0.0000187

AC:

AN:

53386

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.00000450

AC:

AN:

1111402

Other (OTH)

AF:

0.00

AC:

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000469

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Autoinflammatory syndrome

Uncertain:1

Jul 18, 2025

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:curation

The heterozygous p.Arg72Gln variant in FGF7 was identified by our study in 1 individual with autoinflammatory syndrome. While this gene is still lacking sufficient evidence to establish a gene-disease relationship, we believe this is a possible novel gene candidate for autoinflammatory syndrome. Given the limited information about this gene-disease relationship, the significance of the p.Arg72Gln variant is uncertain. If you have any additional information about functional evidence or other individuals with this phenotype that also have variants in FGF7 we encourage you to reach out to us. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.48

BayesDel_addAF

Pathogenic

0.16

BayesDel_noAF

Uncertain

0.0

CADD

Pathogenic

(source)

DANN

Pathogenic

1.0

DEOGEN2

Uncertain

0.72

D;D;.;.

Eigen

Uncertain

0.65

Eigen_PC

Pathogenic

0.70

FATHMM_MKL

Uncertain

0.93

LIST_S2

Uncertain

0.90

.;D;D;D

M_CAP

Pathogenic

0.44

MetaRNN

Uncertain

0.69

D;D;D;D

MetaSVM

Uncertain

0.091

MutationAssessor

Uncertain

2.2

M;M;M;.

PhyloP100

7.4

PrimateAI

Uncertain

0.76

PROVEAN

Benign

-1.0

N;.;N;N

REVEL

Uncertain

0.51

Sift

Benign

0.18

T;.;T;T

Sift4G

Benign

0.29

T;T;T;T

Polyphen

1.0

D;D;.;.

Vest4

0.44

MutPred

0.65

Loss of MoRF binding (P = 0.1068);Loss of MoRF binding (P = 0.1068);Loss of MoRF binding (P = 0.1068);.;

MVP

0.87

MPC

1.9

ClinPred

0.90

GERP RS

5.7

Varity_R

0.27

gMVP

0.86

Mutation Taster

=52/48

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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15-49424512-G-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over