10-101770141-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAA

Variant names:

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

Variant summary

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

The NM_033163.5(FGF8):​c.*186_*187dupTT variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.032 (74 hom., cov: 0)
  • Exomes 𝑓: 0.018 (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 nfe. gnomad4 allele frequency = 0.0322 (3888/120620) while in subpopulation NFE AF= 0.0415 (2428/58498). AF 95% confidence interval is 0.0401. There are 74 homozygotes in gnomad4. There are 1707 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 3888 AD,Digenic gene.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.0322 AC: 3887 AN: 120636 Hom.: 73 Cov.: 0

Gnomad AFR AF: 0.0342

Gnomad AMI AF: 0.0183

Gnomad AMR AF: 0.0146

Gnomad ASJ AF: 0.00529

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00827

Gnomad FIN AF: 0.0203

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0415

Gnomad OTH AF: 0.0266

GnomAD4 exome AF: 0.0183 AC: 4894 AN: 267786 Hom.: 0 Cov.: 0 AF XY: 0.0183 AC XY: 2519 AN XY: 137466

Gnomad4 AFR exome AF: 0.0300

Gnomad4 AMR exome AF: 0.0125

Gnomad4 ASJ exome AF: 0.0103

Gnomad4 EAS exome AF: 0.0107

Gnomad4 SAS exome AF: 0.0118

Gnomad4 FIN exome AF: 0.0150

Gnomad4 NFE exome AF: 0.0204

Gnomad4 OTH exome AF: 0.0192

GnomAD4 genome AF: 0.0322 AC: 3888 AN: 120620 Hom.: 74 Cov.: 0 AF XY: 0.0299 AC XY: 1707 AN XY: 57124

Gnomad4 AFR AF: 0.0342

Gnomad4 AMR AF: 0.0146

Gnomad4 ASJ AF: 0.00529

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00835

Gnomad4 FIN AF: 0.0203

Gnomad4 NFE AF: 0.0415

Gnomad4 OTH AF: 0.0265

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;