rs746870126

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002009.4(FGF7):c.571A>G(p.Met191Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000215 in 1,395,002 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000022 ( 0 hom. )

Consequence

FGF7
NM_002009.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.24

Publications

0 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19527683).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF7	NM_002009.4 link	c.571A>G	p.Met191Val	missense_variant	Exon 4 of 4	ENST00000267843.9	NP_002000.1	P21781-1A0A7U3JVY2
FAM227B	NM_152647.3 link	c.1012+23721T>C		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.571A>G	p.Met191Val	missense_variant	Exon 4 of 4	1	NM_002009.4	ENSP00000267843.4		P21781-1
FAM227B	ENST00000299338.11 link	c.1012+23721T>C		intron_variant	Intron 11 of 15	2	NM_152647.3	ENSP00000299338.6		Q96M60-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.0000146

AC:

AN:

136994

AF XY:

0.0000135

show subpopulations

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:

0.00000215

AC:

AN:

1395002

Hom.:

Cov.:

AF XY:

0.00000144

AC XY:

AN XY:

694220

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30786

American (AMR)

AF:

0.00

AC:

AN:

38224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24264

East Asian (EAS)

AF:

0.00

AC:

AN:

38484

South Asian (SAS)

AF:

0.0000376

AC:

AN:

79732

European-Finnish (FIN)

AF:

0.00

AC:

AN:

37988

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3936

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1083576

Other (OTH)

AF:

0.00

AC:

AN:

58012

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.592

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000854

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 19, 2025

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.571A>G (p.M191V) alteration is located in exon 4 (coding exon 3) of the FGF7 gene. This alteration results from a A to G substitution at nucleotide position 571, causing the methionine (M) at amino acid position 191 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.31

BayesDel_noAF

Benign

-0.45

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Uncertain

0.51

D;D

Eigen

Benign

-0.37

Eigen_PC

Benign

-0.21

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Benign

0.76

.;T

M_CAP

Benign

0.023

MetaRNN

Benign

0.20

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.59

N;N

PhyloP100

2.2

PrimateAI

Benign

0.36

PROVEAN

Benign

-1.0

N;.

REVEL

Benign

0.049

Sift

Benign

0.53

T;.

Sift4G

Benign

0.56

T;T

Polyphen

0.0010

B;B

Vest4

0.22

MutPred

0.45

Loss of disorder (P = 0.0676);Loss of disorder (P = 0.0676);

MVP

0.52

MPC

0.88

ClinPred

0.19

GERP RS

3.2

Varity_R

0.13

gMVP

0.68

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

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rs746870126

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