10-101770141-TA-T

Variant summary

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

The NM_033163.5(FGF8):c.*187del variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (4400 hom., cov: 0)
  • Exomes 𝑓: 0.26 (34 hom.)
• Consequence: FGF8 NM_033163.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.108

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-TA-T is Benign according to our data. Variant chr10-101770141-TA-T is described in ClinVar as [Benign]. Clinvar id is 1263103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

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

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.276 AC: 33242 AN: 120498 Hom.: 4402 Cov.: 0

Gnomad AFR AF: 0.0905

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.262 AC: 69632 AN: 265486 Hom.: 34 Cov.: 0 AF XY: 0.262 AC XY: 35731 AN XY: 136342

Gnomad4 AFR exome AF: 0.213

Gnomad4 AMR exome AF: 0.274

Gnomad4 ASJ exome AF: 0.273

Gnomad4 EAS exome AF: 0.283

Gnomad4 SAS exome AF: 0.276

Gnomad4 FIN exome AF: 0.290

Gnomad4 NFE exome AF: 0.256

Gnomad4 OTH exome AF: 0.268

GnomAD4 genome AF: 0.276 AC: 33230 AN: 120478 Hom.: 4400 Cov.: 0 AF XY: 0.276 AC XY: 15724 AN XY: 57040

Gnomad4 AFR AF: 0.0906

Gnomad4 AMR AF: 0.353

Gnomad4 ASJ AF: 0.294

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.416

Gnomad4 FIN AF: 0.358

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.286

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

Aug 13, 2019

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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;