rs975121

Positions:

• chr3-192179429-G-A
• chr3-192179429-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004113.6(FGF12):​c.229-8773C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.636 in 151,954 control chromosomes in the GnomAD database, including 33,681 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.64 (33681 hom., cov: 32)
• Consequence: FGF12 NM_004113.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.08

Genes affected

FGF12 (HGNC:3668): (fibroblast growth factor 12) 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 growth factor lacks the N-terminal signal sequence present in most of the FGF family members, but it contains clusters of basic residues that have been demonstrated to act as a nuclear localization signal. When transfected into mammalian cells, this protein accumulated in the nucleus, but was not secreted. The specific function of this gene has not yet been determined. [provided by RefSeq, Dec 2019]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.931 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF12	NM_004113.6	c.229-8773C>T		intron_variant		ENST00000445105.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF12	ENST00000445105.7	c.229-8773C>T		intron_variant		1	NM_004113.6	A1

Frequencies

GnomAD3 genomes AF: 0.636 AC: 96593 AN: 151836 Hom.: 33621 Cov.: 32

Gnomad AFR AF: 0.903

Gnomad AMI AF: 0.558

Gnomad AMR AF: 0.637

Gnomad ASJ AF: 0.587

Gnomad EAS AF: 0.953

Gnomad SAS AF: 0.722

Gnomad FIN AF: 0.448

Gnomad MID AF: 0.614

Gnomad NFE AF: 0.477

Gnomad OTH AF: 0.612

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.636 AC: 96707 AN: 151954 Hom.: 33681 Cov.: 32 AF XY: 0.638 AC XY: 47406 AN XY: 74262

Gnomad4 AFR AF: 0.903

Gnomad4 AMR AF: 0.637

Gnomad4 ASJ AF: 0.587

Gnomad4 EAS AF: 0.953

Gnomad4 SAS AF: 0.721

Gnomad4 FIN AF: 0.448

Gnomad4 NFE AF: 0.477

Gnomad4 OTH AF: 0.613

Alfa AF: 0.512 Hom.: 43255

Bravo AF: 0.666

Asia WGS AF: 0.825 AC: 2864 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.8
DANN	Benign	0.30

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: rs975121; hg19: chr3-191897218;