10-101770205-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_033163.5(FGF8):c.*124G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0191 in 908,996 control chromosomes in the GnomAD database, including 242 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (24 hom., cov: 33)
  • Exomes 𝑓: 0.020 (218 hom.)
• Consequence: FGF8 NM_033163.5 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.632

Genes affected

FGF8 (HGNC:3686): (fibroblast growth factor 8) 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 known to be a factor that supports androgen and anchorage independent growth of mammary tumor cells. Overexpression of this gene has been shown to increase tumor growth and angiogensis. The adult expression of this gene is restricted to testes and ovaries. Temporal and spatial pattern of this gene expression suggests its function as an embryonic epithelial factor. Studies of the mouse and chick homologs revealed roles in midbrain and limb development, organogenesis, embryo gastrulation and left-right axis determination. The alternative splicing of this gene results in four transcript variants. [provided by RefSeq, Jul 2008]

LOC105378457 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 10-101770205-C-G is Benign according to our data. Variant chr10-101770205-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1219940.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0153 (2327/152138) while in subpopulation NFE AF= 0.0255 (1732/67966). AF 95% confidence interval is 0.0245. There are 24 homozygotes in gnomad4. There are 1054 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 2328 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF8	NM_033163.5	c.*124G>C		3_prime_UTR_variant	6/6	ENST00000320185.7
LOC105378457	XR_007062268.1	n.138-352C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF8	ENST00000320185.7	c.*124G>C		3_prime_UTR_variant	6/6	1	NM_033163.5	A2
FGF8	ENST00000344255.8	c.*124G>C		3_prime_UTR_variant	6/6	1
FGF8	ENST00000469792.6	c.*823G>C		3_prime_UTR_variant, NMD_transcript_variant	5/5	5
FGF8	ENST00000618991.5			downstream_gene_variant		3

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2328 AN: 152024 Hom.: 24 Cov.: 33

Gnomad AFR AF: 0.00493

Gnomad AMI AF: 0.0176

Gnomad AMR AF: 0.00864

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00290

Gnomad FIN AF: 0.0150

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.0255

Gnomad OTH AF: 0.0110

GnomAD4 exome AF: 0.0198 AC: 15015 AN: 756858 Hom.: 218 Cov.: 10 AF XY: 0.0192 AC XY: 7272 AN XY: 378006

Gnomad4 AFR exome AF: 0.00358

Gnomad4 AMR exome AF: 0.00720

Gnomad4 ASJ exome AF: 0.0119

Gnomad4 EAS exome AF: 0.0000319

Gnomad4 SAS exome AF: 0.00260

Gnomad4 FIN exome AF: 0.0199

Gnomad4 NFE exome AF: 0.0238

Gnomad4 OTH exome AF: 0.0160

GnomAD4 genome AF: 0.0153 AC: 2327 AN: 152138 Hom.: 24 Cov.: 33 AF XY: 0.0142 AC XY: 1054 AN XY: 74370

Gnomad4 AFR AF: 0.00491

Gnomad4 AMR AF: 0.00863

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.0150

Gnomad4 NFE AF: 0.0255

Gnomad4 OTH AF: 0.0109

Alfa AF: 0.0193 Hom.: 3

Bravo AF: 0.0153

Asia WGS AF: 0.00346 AC: 12 AN: 3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 14, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
Cadd	Benign	1.8
Dann	Benign	0.73

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs3218239; hg19: chr10-103529962;