chr10-101770141-TA-T

Variant names:

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

Variant summary

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

The NM_033163.5(FGF8):​c.*187delT 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 0.28 (4400 hom., cov: 0)
  • Exomes 𝑓: 0.26 (34 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-TA-T is Benign according to our data. Variant chr10-101770141-TA-T is described in ClinVar as Benign. ClinVar VariationId is 1263103.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

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

Frequencies

GnomAD3 genomes AF: 0.276 AC: 33242 AN: 120498 Hom.: 4402 Cov.: 0

Gnomad AFR AF: 0.0905

Gnomad AMI AF: 0.355

Gnomad AMR AF: 0.352

Gnomad ASJ AF: 0.294

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.416

Gnomad FIN AF: 0.358

Gnomad MID AF: 0.296

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.262 AC: 69632 AN: 265486 Hom.: 34 Cov.: 0 AF XY: 0.262 AC XY: 35731 AN XY: 136342

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

African (AFR) AF: 0.213 AC: 1562 AN: 7332

American (AMR) AF: 0.274 AC: 2622 AN: 9560

Ashkenazi Jewish (ASJ) AF: 0.273 AC: 2418 AN: 8872

East Asian (EAS) AF: 0.283 AC: 6002 AN: 21242

South Asian (SAS) AF: 0.276 AC: 4128 AN: 14966

European-Finnish (FIN) AF: 0.290 AC: 5600 AN: 19294

Middle Eastern (MID) AF: 0.256 AC: 314 AN: 1226

European-Non Finnish (NFE) AF: 0.256 AC: 42648 AN: 166782

Other (OTH) AF: 0.268 AC: 4338 AN: 16212

⚠️ 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: 0.276 AC: 33230 AN: 120478 Hom.: 4400 Cov.: 0 AF XY: 0.276 AC XY: 15724 AN XY: 57040

African (AFR) AF: 0.0906 AC: 2862 AN: 31606

American (AMR) AF: 0.353 AC: 4249 AN: 12050

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 889 AN: 3020

East Asian (EAS) AF: 0.270 AC: 1138 AN: 4218

South Asian (SAS) AF: 0.416 AC: 1544 AN: 3712

European-Finnish (FIN) AF: 0.358 AC: 1703 AN: 4760

Middle Eastern (MID) AF: 0.320 AC: 71 AN: 222

European-Non Finnish (NFE) AF: 0.343 AC: 20017 AN: 58434

Other (OTH) AF: 0.286 AC: 474 AN: 1658

Alfa AF: 0.111 Hom.: 142

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 13, 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;