rs6775137

Variant names:

• chr3-192449360-C-A
• rs6775137
• NM_004113.6:c.14-88822G>T

Your query was ambiguous. Multiple possible variants found:

• chr3-192449360-C-A
• chr3-192449360-C-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004113.6(FGF12):​c.14-88822G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.364 in 151,922 control chromosomes in the GnomAD database, including 12,068 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 0.36 (12068 hom., cov: 31)
• Consequence: FGF12 NM_004113.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.420
• Publications: 2 publications found

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]

FGF12 Gene-Disease associations (from GenCC):

• developmental and epileptic encephalopathy, 47

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• undetermined early-onset epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.477 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF12	NM_004113.6	c.14-88822G>T		intron_variant	Intron 2 of 5	ENST00000445105.7	NP_004104.3
FGF12	NM_001377293.1	c.-59-88822G>T		intron_variant	Intron 1 of 4		NP_001364222.1
FGF12	NM_001377292.1	c.14-113896G>T		intron_variant	Intron 2 of 4		NP_001364221.1
FGF12	XM_005247227.3	c.91+65307G>T		intron_variant	Intron 1 of 4		XP_005247284.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF12	ENST00000445105.7	c.14-88822G>T		intron_variant	Intron 2 of 5	1	NM_004113.6	ENSP00000393686.1

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55235 AN: 151806 Hom.: 12070 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.446

Gnomad AMR AF: 0.462

Gnomad ASJ AF: 0.558

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.406

Gnomad FIN AF: 0.395

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.481

Gnomad OTH AF: 0.409

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

GnomAD4 genome AF: 0.364 AC: 55235 AN: 151922 Hom.: 12068 Cov.: 31 AF XY: 0.362 AC XY: 26880 AN XY: 74238

African (AFR) AF: 0.119 AC: 4943 AN: 41474

American (AMR) AF: 0.462 AC: 7053 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.558 AC: 1935 AN: 3466

East Asian (EAS) AF: 0.203 AC: 1046 AN: 5146

South Asian (SAS) AF: 0.407 AC: 1954 AN: 4798

European-Finnish (FIN) AF: 0.395 AC: 4168 AN: 10540

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.481 AC: 32706 AN: 67926

Other (OTH) AF: 0.405 AC: 854 AN: 2108

Alfa AF: 0.456 Hom.: 29927

Bravo AF: 0.357

Asia WGS AF: 0.276 AC: 960 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.2
DANN	Benign	0.61
PhyloP100		-0.42
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs6775137; hg19: chr3-192167149;