10-101770141-TAAAAAAAAAAAAAAA-TAAAAAAAAAAAAAAAA

Variant names:

• chr10-101770141-T-TA
• rs11322844
• NM_033163.5:c.*187dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_033163.5(FGF8):​c.*187dupT 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
• Publications: 1 publications found

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]

FGF8 Gene-Disease associations (from GenCC):

• hypogonadotropic hypogonadism 6 with or without anosmia

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• hypogonadotropic hypogonadism

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• holoprosencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000308881 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
FGF8	NM_033163.5	c.*187dupT		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	ENST00000320185.7	c.*187dupT		3_prime_UTR_variant	Exon 6 of 6	1	NM_033163.5	ENSP00000321797.2

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.131 AC: 964 AN: 7344

American (AMR) AF: 0.0661 AC: 636 AN: 9628

Ashkenazi Jewish (ASJ) AF: 0.0867 AC: 768 AN: 8860

East Asian (EAS) AF: 0.0866 AC: 1835 AN: 21190

South Asian (SAS) AF: 0.0670 AC: 1002 AN: 14966

European-Finnish (FIN) AF: 0.0631 AC: 1219 AN: 19328

Middle Eastern (MID) AF: 0.0843 AC: 103 AN: 1222

European-Non Finnish (NFE) AF: 0.0701 AC: 11778 AN: 168132

Other (OTH) AF: 0.0763 AC: 1241 AN: 16272

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0809 AC: 2556 AN: 31602

American (AMR) AF: 0.0239 AC: 289 AN: 12094

Ashkenazi Jewish (ASJ) AF: 0.0334 AC: 101 AN: 3024

East Asian (EAS) AF: 0.0109 AC: 46 AN: 4216

South Asian (SAS) AF: 0.0186 AC: 69 AN: 3712

European-Finnish (FIN) AF: 0.00689 AC: 33 AN: 4792

Middle Eastern (MID) AF: 0.0177 AC: 4 AN: 226

European-Non Finnish (NFE) AF: 0.0292 AC: 1710 AN: 58564

Other (OTH) AF: 0.0386 AC: 64 AN: 1660

Alfa AF: 0.0187 Hom.: 142

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.11

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11322844; hg19: chr10-103529898;