chr10-101770141-TAAAAAAAAAAAA-T

Variant names:

• chr10-101770141-TAAAAAAAAAAAA-T
• rs11322844
• NM_033163.5:c.*176_*187delTTTTTTTTTTTT

Variant summary

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

The NM_033163.5(FGF8):​c.*176_*187delTTTTTTTTTTTT variant causes a 3 prime UTR change. The variant allele was found at a frequency of 0.0511 in 393,080 control chromosomes in the GnomAD database, including 465 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.044 (147 hom., cov: 0)
  • Exomes 𝑓: 0.054 (318 hom.)
• Consequence: FGF8 NM_033163.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 4.86
• 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-TAAAAAAAAAAAA-T is Benign according to our data. Variant chr10-101770141-TAAAAAAAAAAAA-T is described in ClinVar as Benign. ClinVar VariationId is 1269222.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0588 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FGF8	NM_033163.5	c.*176_*187delTTTTTTTTTTTT		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.*176_*187delTTTTTTTTTTTT		3_prime_UTR_variant	Exon 6 of 6	1	NM_033163.5	ENSP00000321797.2

Frequencies

GnomAD3 genomes AF: 0.0438 AC: 5288 AN: 120832 Hom.: 146 Cov.: 0

Gnomad AFR AF: 0.0138

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.0501

Gnomad ASJ AF: 0.0162

Gnomad EAS AF: 0.000708

Gnomad SAS AF: 0.0168

Gnomad FIN AF: 0.0607

Gnomad MID AF: 0.0123

Gnomad NFE AF: 0.0605

Gnomad OTH AF: 0.0375

GnomAD4 exome AF: 0.0544 AC: 14807 AN: 272266 Hom.: 318 AF XY: 0.0535 AC XY: 7473 AN XY: 139806

African (AFR) AF: 0.0104 AC: 78 AN: 7506

American (AMR) AF: 0.0481 AC: 471 AN: 9790

Ashkenazi Jewish (ASJ) AF: 0.0188 AC: 171 AN: 9076

East Asian (EAS) AF: 0.0000923 AC: 2 AN: 21674

South Asian (SAS) AF: 0.0291 AC: 441 AN: 15132

European-Finnish (FIN) AF: 0.0451 AC: 888 AN: 19700

Middle Eastern (MID) AF: 0.0104 AC: 13 AN: 1248

European-Non Finnish (NFE) AF: 0.0700 AC: 12007 AN: 171496

Other (OTH) AF: 0.0442 AC: 736 AN: 16644

GnomAD4 genome AF: 0.0438 AC: 5291 AN: 120814 Hom.: 147 Cov.: 0 AF XY: 0.0438 AC XY: 2508 AN XY: 57224

African (AFR) AF: 0.0138 AC: 435 AN: 31612

American (AMR) AF: 0.0504 AC: 611 AN: 12112

Ashkenazi Jewish (ASJ) AF: 0.0162 AC: 49 AN: 3022

East Asian (EAS) AF: 0.000711 AC: 3 AN: 4218

South Asian (SAS) AF: 0.0170 AC: 63 AN: 3714

European-Finnish (FIN) AF: 0.0607 AC: 292 AN: 4810

Middle Eastern (MID) AF: 0.0133 AC: 3 AN: 226

European-Non Finnish (NFE) AF: 0.0605 AC: 3545 AN: 58618

Other (OTH) AF: 0.0373 AC: 62 AN: 1662

Alfa AF: 0.0227 Hom.: 142

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 14, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		4.9

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;