chr15-49424350-G-A

Position:

• chr15-49424350-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_002009.4(FGF7):​c.53G>A​(p.Cys18Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 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: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FGF7 NM_002009.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.54

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]

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08545375).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF7	NM_002009.4	c.53G>A	p.Cys18Tyr	missense_variant	2/4	ENST00000267843.9	NP_002000.1
FAM227B	NM_152647.3	c.1013-52951C>T		intron_variant		ENST00000299338.11	NP_689860.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF7	ENST00000267843.9	c.53G>A	p.Cys18Tyr	missense_variant	2/4	1	NM_002009.4	ENSP00000267843	P1
FAM227B	ENST00000299338.11	c.1013-52951C>T		intron_variant		2	NM_152647.3	ENSP00000299338	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1461444 Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0 AN XY: 727030

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.53G>A (p.C18Y) alteration is located in exon 2 (coding exon 1) of the FGF7 gene. This alteration results from a G to A substitution at nucleotide position 53, causing the cysteine (C) at amino acid position 18 to be replaced by a tyrosine (Y). 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	0.078
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	14
DANN	Benign	0.78
DEOGEN2	Benign	0.37	T;T;.
Eigen	Benign	-0.38
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.65	.;T;T
M_CAP	Benign	0.0011	T
MetaRNN	Benign	0.085	T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	-1.0	N;N;N
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Benign	0.43	T
PROVEAN	Benign	-0.17	N;.;N
REVEL	Benign	0.089
Sift	Benign	0.42	T;.;T
Sift4G	Benign	0.99	T;T;T
Polyphen		0.0	B;B;.
Vest4		0.15
MutPred		0.65		Gain of catalytic residue at C18 (P = 0.1033);Gain of catalytic residue at C18 (P = 0.1033);Gain of catalytic residue at C18 (P = 0.1033);
MVP		0.17
MPC		1.4
ClinPred		0.17	T
GERP RS		3.7
Varity_R		0.054
gMVP		0.48

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr15-49716547;