Variant 11-69774016-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_ModerateBP6_ModerateBS1BS2

The NM_002007.4(FGF4):c.444+8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000937 in 1,608,416 control chromosomes in the GnomAD database, including 15 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0050 ( 7 hom., cov: 34)

Exomes 𝑓: 0.00052 ( 8 hom. )

Consequence

FGF4
NM_002007.4 splice_region, intron

Scores

Splicing: ADA: 0.01887

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.392

Variant links:

Genes affected

FGF4 (HGNC:3682): (fibroblast growth factor 4) 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 gene was identified by its oncogenic transforming activity. This gene and FGF3, another oncogenic growth factor, are located closely on chromosome 11. Co-amplification of both genes was found in various kinds of human tumors. Studies on the mouse homolog suggested a function in bone morphogenesis and limb development through the sonic hedgehog (SHH) signaling pathway. [provided by RefSeq, Jul 2008]

FGF4 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.23).

BP6

Variant 11-69774016-G-A is Benign according to our data. Variant chr11-69774016-G-A is described in ClinVar as [Benign]. Clinvar id is 776637.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00496 (756/152358) while in subpopulation AFR AF= 0.0177 (736/41588). AF 95% confidence interval is 0.0166. There are 7 homozygotes in gnomad4. There are 346 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 756 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF4	NM_002007.4 linkuse as main transcript	c.444+8C>T		splice_region_variant, intron_variant		ENST00000168712.3	NP_001998.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF4	ENST00000168712.3 linkuse as main transcript	c.444+8C>T		splice_region_variant, intron_variant		1	NM_002007.4	ENSP00000168712	P1	P08620-1
FGF4	ENST00000538040.1 linkuse as main transcript	n.421-531C>T		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes

AF:

0.00495

AC:

754

AN:

152240

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0177

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000850

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00114

AC:

278

AN:

243184

Hom.:

AF XY:

0.000771

AC XY:

102

AN XY:

132368

show subpopulations

Gnomad AFR exome

AF:

0.0168

Gnomad AMR exome

AF:

0.000469

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000183

Gnomad OTH exome

AF:

0.000509

GnomAD4 exome

AF:

0.000516

AC:

751

AN:

1456058

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

332

AN XY:

724410

show subpopulations

Gnomad4 AFR exome

AF:

0.0197

Gnomad4 AMR exome

AF:

0.000562

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000467

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000541

Gnomad4 OTH exome

AF:

0.000898

GnomAD4 genome

AF:

0.00496

AC:

756

AN:

152358

Hom.:

Cov.:

AF XY:

0.00464

AC XY:

346

AN XY:

74494

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.000849

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00249

Hom.:

Bravo

AF:

0.00563

Asia WGS

AF:

0.00173

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Aug 16, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.23

CADD

Benign

7.1

DANN

Benign

0.95

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.019

dbscSNV1_RF

Benign

0.030

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over