chr10-101770141-TAA-T

Variant names:

• chr10-101770141-TAA-T
• rs11322844
• NM_033163.5:c.*186_*187delTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_033163.5(FGF8):​c.*186_*187delTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 382,198 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0031 (2 hom., cov: 0)
  • Exomes 𝑓: 0.11 (0 hom.)
• Consequence: FGF8 NM_033163.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• 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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.141 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF8	NM_033163.5	c.*186_*187delTT		3_prime_UTR_variant	Exon 6 of 6	ENST00000320185.7	NP_149353.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FGF8	ENST00000320185	c.*186_*187delTT		3_prime_UTR_variant	Exon 6 of 6	1	NM_033163.5	ENSP00000321797.2
FGF8	ENST00000344255	c.*186_*187delTT		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000340039.3
FGF8	ENST00000469792.6	n.*885_*886delTT		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	5		ENSP00000473299.1
FGF8	ENST00000469792.6	n.*885_*886delTT		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000473299.1

Frequencies

GnomAD3 genomes AF: 0.00312 AC: 377 AN: 120762 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00678

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00157

Gnomad ASJ AF: 0.00166

Gnomad EAS AF: 0.00142

Gnomad SAS AF: 0.00240

Gnomad FIN AF: 0.00146

Gnomad MID AF: 0.0123

Gnomad NFE AF: 0.00191

Gnomad OTH AF: 0.00121

GnomAD4 exome AF: 0.110 AC: 28647 AN: 261454 Hom.: 0 AF XY: 0.111 AC XY: 14898 AN XY: 134426

Gnomad4 AFR exome AF: 0.0767

Gnomad4 AMR exome AF: 0.130

Gnomad4 ASJ exome AF: 0.101

Gnomad4 EAS exome AF: 0.105

Gnomad4 SAS exome AF: 0.146

Gnomad4 FIN exome AF: 0.123

Gnomad4 NFE exome AF: 0.106

Gnomad4 OTH exome AF: 0.110

GnomAD4 genome AF: 0.00313 AC: 378 AN: 120744 Hom.: 2 Cov.: 0 AF XY: 0.00344 AC XY: 197 AN XY: 57194

Gnomad4 AFR AF: 0.00680

Gnomad4 AMR AF: 0.00165

Gnomad4 ASJ AF: 0.00166

Gnomad4 EAS AF: 0.00142

Gnomad4 SAS AF: 0.00216

Gnomad4 FIN AF: 0.00146

Gnomad4 NFE AF: 0.00193

Gnomad4 OTH AF: 0.00120

ClinVar

Not reported in ClinVar

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;