10-101770141-TAAAAAAAAAAAAAAA-TAAAAAAAAAAA

Variant names:

• chr10-101770141-TAAAA-T
• rs11322844
• NM_033163.5:c.*184_*187delTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_033163.5(FGF8):​c.*184_*187delTTTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00159 in 391,750 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0000083 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0023 (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.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0023 (623/270976) while in subpopulation SAS AF= 0.00479 (72/15040). AF 95% confidence interval is 0.0039. There are 0 homozygotes in gnomad4_exome. There are 344 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 623 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF8	NM_033163.5	c.*184_*187delTTTT		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.*184_*187delTTTT		3_prime_UTR_variant	Exon 6 of 6	1	NM_033163.5	ENSP00000321797.2
FGF8	ENST00000344255	c.*184_*187delTTTT		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000340039.3
FGF8	ENST00000469792.6	n.*883_*886delTTTT		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	5		ENSP00000473299.1
FGF8	ENST00000469792.6	n.*883_*886delTTTT		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000473299.1

Frequencies

GnomAD3 genomes AF: 0.00000828 AC: 1 AN: 120774 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000171

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00230 AC: 623 AN: 270976 Hom.: 0 AF XY: 0.00247 AC XY: 344 AN XY: 139128

Gnomad4 AFR exome AF: 0.00120

Gnomad4 AMR exome AF: 0.00247

Gnomad4 ASJ exome AF: 0.00243

Gnomad4 EAS exome AF: 0.00186

Gnomad4 SAS exome AF: 0.00479

Gnomad4 FIN exome AF: 0.00291

Gnomad4 NFE exome AF: 0.00214

Gnomad4 OTH exome AF: 0.00187

GnomAD4 genome AF: 0.00000828 AC: 1 AN: 120774 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 57200

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000171

Gnomad4 OTH AF: 0.00

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;