10-101770141-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAAAA

Variant names:

• chr10-101770141-T-TAAA
• rs11322844
• NM_033163.5:c.*185_*187dupTTT

Variant summary

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

The NM_033163.5(FGF8):​c.*185_*187dupTTT 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 0.00025 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0030 (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 = 0.000248 (30/120760) while in subpopulation NFE AF= 0.000358 (21/58592). AF 95% confidence interval is 0.000239. There are 0 homozygotes in gnomad4. There are 15 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 30 AD,Digenic gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF8	NM_033163.5	c.*185_*187dupTTT		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.*185_*187dupTTT		3_prime_UTR_variant	Exon 6 of 6	1	NM_033163.5	ENSP00000321797.2
FGF8	ENST00000344255	c.*185_*187dupTTT		3_prime_UTR_variant	Exon 6 of 6	1		ENSP00000340039.3
FGF8	ENST00000469792.6	n.*884_*886dupTTT		splice_region_variant, non_coding_transcript_exon_variant	Exon 5 of 5	5		ENSP00000473299.1
FGF8	ENST00000469792.6	n.*884_*886dupTTT		3_prime_UTR_variant	Exon 5 of 5	5		ENSP00000473299.1

Frequencies

GnomAD3 genomes AF: 0.000248 AC: 30 AN: 120778 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000248

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000267

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000358

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00297 AC: 805 AN: 271022 Hom.: 0 Cov.: 0 AF XY: 0.00302 AC XY: 421 AN XY: 139178

Gnomad4 AFR exome AF: 0.00616

Gnomad4 AMR exome AF: 0.00184

Gnomad4 ASJ exome AF: 0.00111

Gnomad4 EAS exome AF: 0.000879

Gnomad4 SAS exome AF: 0.00186

Gnomad4 FIN exome AF: 0.00229

Gnomad4 NFE exome AF: 0.00352

Gnomad4 OTH exome AF: 0.00224

GnomAD4 genome AF: 0.000248 AC: 30 AN: 120760 Hom.: 0 Cov.: 0 AF XY: 0.000262 AC XY: 15 AN XY: 57200

Gnomad4 AFR AF: 0.000158

Gnomad4 AMR AF: 0.000248

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000269

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000358

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;