10-101770141-T-TA

Position:

• chr10-101770141-T-TA

Variant summary

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

The NM_033163.5(FGF8):​c.*187_*188insT 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 0.041 (121 hom., cov: 0)
  • Exomes 𝑓: 0.073 (0 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-T-TA is Benign according to our data. Variant chr10-101770141-T-TA is described in ClinVar as [Benign]. Clinvar id is 1251743.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FGF8	NM_033163.5	c.*187_*188insT		3_prime_UTR_variant	6/6	ENST00000320185.7
LOC105378457	XR_007062268.1	n.138-393dup		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FGF8	ENST00000320185.7	c.*187_*188insT		3_prime_UTR_variant	6/6	1	NM_033163.5	A2
FGF8	ENST00000344255.8	c.*187_*188insT		3_prime_UTR_variant	6/6	1
FGF8	ENST00000469792.6			downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.0405 AC: 4886 AN: 120730 Hom.: 121 Cov.: 0

Gnomad AFR AF: 0.0808

Gnomad AMI AF: 0.0207

Gnomad AMR AF: 0.0239

Gnomad ASJ AF: 0.0334

Gnomad EAS AF: 0.0111

Gnomad SAS AF: 0.0187

Gnomad FIN AF: 0.00689

Gnomad MID AF: 0.0164

Gnomad NFE AF: 0.0292

Gnomad OTH AF: 0.0387

GnomAD4 exome AF: 0.0732 AC: 19546 AN: 266942 Hom.: 0 Cov.: 0 AF XY: 0.0727 AC XY: 9971 AN XY: 137084

Gnomad4 AFR exome AF: 0.131

Gnomad4 AMR exome AF: 0.0661

Gnomad4 ASJ exome AF: 0.0867

Gnomad4 EAS exome AF: 0.0866

Gnomad4 SAS exome AF: 0.0670

Gnomad4 FIN exome AF: 0.0631

Gnomad4 NFE exome AF: 0.0701

Gnomad4 OTH exome AF: 0.0763

GnomAD4 genome AF: 0.0405 AC: 4889 AN: 120710 Hom.: 121 Cov.: 0 AF XY: 0.0388 AC XY: 2220 AN XY: 57174

Gnomad4 AFR AF: 0.0809

Gnomad4 AMR AF: 0.0239

Gnomad4 ASJ AF: 0.0334

Gnomad4 EAS AF: 0.0109

Gnomad4 SAS AF: 0.0186

Gnomad4 FIN AF: 0.00689

Gnomad4 NFE AF: 0.0292

Gnomad4 OTH AF: 0.0386

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 21, 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;