10-101770141-TAAAAAAAAAAAA-T

Position:

• chr10-101770141-TAAAAAAAAAAAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_033163.5(FGF8):​c.*176_*187del variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0511 in 393,080 control chromosomes in the GnomAD database, including 465 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (147 hom., cov: 0)
  • Exomes 𝑓: 0.054 (318 hom.)
• Consequence: FGF8 NM_033163.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.86

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 -10 ACMG points.

• BP6: Variant 10-101770141-TAAAAAAAAAAAA-T is Benign according to our data. Variant chr10-101770141-TAAAAAAAAAAAA-T is described in ClinVar as [Benign]. Clinvar id is 1269222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FGF8	NM_033163.5	c.*176_*187del		3_prime_UTR_variant	6/6	ENST00000320185.7	NP_149353.1
LOC105378457	XR_007062268.1	n.138-404_138-393del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FGF8	ENST00000320185.7	c.*176_*187del		3_prime_UTR_variant	6/6	1	NM_033163.5	ENSP00000321797	A2
FGF8	ENST00000344255.8	c.*176_*187del		3_prime_UTR_variant	6/6	1		ENSP00000340039
FGF8	ENST00000469792.6	c.*875_*886del		3_prime_UTR_variant, NMD_transcript_variant	5/5	5		ENSP00000473299

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 5288 AN: 120832 Hom.: 146 Cov.: 0

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.0501

Gnomad ASJ AF: 0.0162

Gnomad EAS AF: 0.000708

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0123

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.0375

GnomAD4 exome AF: 0.0544 AC: 14807 AN: 272266 Hom.: 318 AF XY: 0.0535 AC XY: 7473 AN XY: 139806

Gnomad4 AFR exome AF: 0.0104

Gnomad4 AMR exome AF: 0.0481

Gnomad4 ASJ exome AF: 0.0188

Gnomad4 EAS exome AF: 0.0000923

Gnomad4 SAS exome AF: 0.0291

Gnomad4 FIN exome AF: 0.0451

Gnomad4 NFE exome AF: 0.0700

Gnomad4 OTH exome AF: 0.0442

GnomAD4 genome AF: 0.0438 AC: 5291 AN: 120814 Hom.: 147 Cov.: 0 AF XY: 0.0438 AC XY: 2508 AN XY: 57224

Gnomad4 AFR AF: 0.0138

Gnomad4 AMR AF: 0.0504

Gnomad4 ASJ AF: 0.0162

Gnomad4 EAS AF: 0.000711

Gnomad4 SAS AF: 0.0170

Gnomad4 FIN AF: 0.0607

Gnomad4 NFE AF: 0.0605

Gnomad4 OTH AF: 0.0373

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 14, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11322844; hg19: chr10-103529898;